トップ›研究者一覧›米村重信

研究者を探す

研究者にアプローチする
更新情報を通知する

米村重信

徳島大学

プロフィール
教育活動
研究活動
社会活動
リサーチマップ・
Jグローバル
KAKEN
注目研究

研究者総覧で最新データを確認する

2024年5月8日更新

職名: 教授
電話: 088-633-7055
電子メール: yonemura.shigenobu@tokushima-u.ac.jp
学歴: 1988/3: 東京大学大学院理学系研究科博士課程 (生物化学専攻) 終了
学位: 理学博士 (東京大学大学院理学系研究科生物化学専攻) (1988年3月)
職歴・経歴: 2014/11: 理化学研究所ライフサイエンス技術基盤センター超微形態研究チームチームリーダー

専門分野・研究分野: 細胞生物学

研究者総覧で最新データを確認する

2024年5月8日更新

専門分野・研究分野: 細胞生物学
担当経験のある授業科目: コミュニケーション特論 (大学院)
コミュニケーション特論(Communication Know-How) (大学院)
ナノテクノロジー医療応用特論 (大学院)
ヒューマンサイエンス(形態と機能) (大学院)
ヒューマンサイエンス(形態と機能学) (大学院)
先端医学 (学部)
医学概論 (共通教育)
医療遺伝学特論 (大学院)
国際統合医療特論 (大学院)
国際統合医療特論(Global Topics of Interdisciplinary Health Care) (大学院)
基礎化学 (共通教育)
基礎医学 (学部)
基礎医学統合実習 (学部)
基礎生物学M (共通教育)
技術英語入門 (学部)
検査機器総論 (学部)
生化学 (学部)
生化学・生化学実習 (学部)
生化学入門 (共通教育)
生命科学コミュニケーション特論 (大学院)
生命科学コミュニケーション特論 (Communication Know-How) (大学院)
病態予防医学実験実習・臨床研究実習 (大学院)
発生・分化・再生医学特論 (大学院)
研究室配属 (学部)
細胞生物学 (大学院)
細胞生物学演習 (大学院)
指導経験: 1人 (修士), 1人 (博士)

研究者総覧で最新データを確認する

2024年5月8日更新

専門分野・研究分野: 細胞生物学

研究テーマ: 上皮極性と上皮形態形成

著書

米村重信 :
細胞間接着のメカノバイオロジー,
2015年.

論文

H Nishida, AB Albero, K Onoue, Y Ikegawa, S Sulekh, U Sakizli, Y Minami, Shigenobu Yonemura, YC Wang and SK Yoo :
Necrosensor: a genetically encoded fluorescent sensor for visualizing necrosis in Drosophila.,
Biology Open, 2023. A Kira, I Tatsutomi, K Saito, M Murata, I Hattori, H Kajita, N Muraki, Y Oda, S Satoh, Y Tsukamoto, S Kimura, K Onoue, Shigenobu Yonemura, S Arakawa, H Kato, T Hirashima and K Kawane :
Apoptotic extracellular vesicle formation via local phosphatidylserine exposure drives efficient cell extrusion.,
Developmental Cell, Vol.58, No.14, 1282-1298, 2023. K Fukuda, T Shimi, C Shimura, T Ono, T Suzuki, K Onoue, S Okayama, H Miura, I Hiratani, K Ikeda, Y Okada, N Dohmae, Shigenobu Yonemura, A Inoue, H Kimura and Y Shinkai :
Epigenetic plasticity safeguards heterochromatin configuration in mammals.,
Nucleic Acids Research, Vol.51, No.12, 6190-6207, 2023.

(要約): Heterochromatin is a key architectural feature of eukaryotic chromosomes critical for cell type-specific gene expression and genome stability. In the mammalian nucleus, heterochromatin segregates from transcriptionally active genomic regions and exists in large, condensed, and inactive nuclear compartments. However, the mechanisms underlying the spatial organization of heterochromatin need to be better understood. Histone H3 lysine 9 trimethylation (H3K9me3) and lysine 27 trimethylation (H3K27me3) are two major epigenetic modifications that enrich constitutive and facultative heterochromatin, respectively. Mammals have at least five H3K9 methyltransferases (SUV39H1, SUV39H2, SETDB1, G9a and GLP) and two H3K27 methyltransferases (EZH1 and EZH2). In this study, we addressed the role of H3K9 and H3K27 methylation in heterochromatin organization using a combination of mutant cells for five H3K9 methyltransferases and an EZH1/2 dual inhibitor, DS3201. We showed that H3K27me3, which is normally segregated from H3K9me3, was redistributed to regions targeted by H3K9me3 after the loss of H3K9 methylation and that the loss of both H3K9 and H3K27 methylation resulted in impaired condensation and spatial organization of heterochromatin. Our data demonstrate that the H3K27me3 pathway safeguards heterochromatin organization after the loss of H3K9 methylation in mammalian cells.
(キーワード): Animals / Epigenesis, Genetic / Heterochromatin / Histones / Lysine / Mammals / Methylation / Histone Methyltransferases
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/nar/gkad387
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37178005; ● Search Scopus @ Elsevier (PMID): 37178005; ● Search Scopus @ Elsevier (DOI): 10.1093/nar/gkad387

(DOI: 10.1093/nar/gkad387, PubMed: 37178005) Takayuki Onai, Toshihiro Aramaki, Akira Takai, Kisa Kakiguchi and Shigenobu Yonemura :
Cranial cartilages: Players in the evolution of the cranium during evolution of the chordates in general and of the vertebrates in particular.,
Evolution & Development, Vol.25, No.3, 197-208, 2023.

(要約): The present contribution is chiefly a review, augmented by some new results on amphioxus and lamprey anatomy, that draws on paleontological and developmental data to suggest a scenario for cranial cartilage evolution in the phylum chordata. Consideration is given to the cartilage-related tissues of invertebrate chordates (amphioxus and some fossil groups like vetulicolians) as well as in the two major divisions of the subphylum Vertebrata (namely, agnathans, and gnathostomes). In the invertebrate chordates, which can be considered plausible proxy ancestors of the vertebrates, only a viscerocranium is present, whereas a neurocranium is absent. For this situation, we examine how cartilage-related tissues of this head region prefigure the cellular cartilage types in the vertebrates. We then focus on the vertebrate neurocranium, where cyclostomes evidently lack neural-crest derived trabecular cartilage (although this point needs to be established more firmly). In the more complex gnathostome, several neural-crest derived cartilage types are present: namely, the trabecular cartilages of the prechordal region and the parachordal cartilage the chordal region. In sum, we present an evolutionary framework for cranial cartilage evolution in chordates and suggest aspects of the subject that should profit from additional study.
(キーワード): Animals / Vertebrates / Skull / Cartilage / Neural Crest / Lancelets / Biological Evolution
(徳島大学機関リポジトリ): ● Metadata: 118728
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/ede.12433
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36946416; ● Search Scopus @ Elsevier (PMID): 36946416; ● Search Scopus @ Elsevier (DOI): 10.1111/ede.12433

(徳島大学機関リポジトリ: 118728, DOI: 10.1111/ede.12433, PubMed: 36946416) Aya Tentaku, Shusaku Kurisu, Kurumi Sejima, Toshiki Nagao, Akira Takahashi and Shigenobu Yonemura :
Proximal deposition of collagen IV by fibroblasts contributes to basement membrane formation by colon epithelial cells invitro.,
The FEBS Journal, Vol.289, No.23, 7466-7485, 2022.

(要約): The basement membrane (BM) underlying epithelial tissue is a thin layer of extracellular matrix that governs tissue integrity and function. Epithelial BMs are generally assembled using BM components secreted from two origins: epithelium and stroma. Although denovo BM formation involves self-assembly processes of large proteins, it remains unclear how stroma-derived macromolecules are transported and assembled, specifically in the BM region. In this study, we established an invitro co-culture model of BM formation in which DLD-1 human colon epithelial cells were cultured on top of collagen I gel containing human embryonic OUMS-36T-2 fibroblasts as stromal cells. A distinct feature of our system is represented by OUMS-36T-2 cells which are almost exclusively responsible for synthesis of collagen IV, a major BM component. Exploiting this advantage, we found that collagen IV incorporation was significantly impaired in culture conditions where OUMS-36T-2 cells were not allowed to directly contact DLD-1 cells. Soluble collagen IV, once diluted in the culture medium, did not accumulate in the BM region efficiently. Live imaging of fluorescently tagged collagen IV revealed that OUMS-36T-2 cells deposited collagen IV aggregates directly onto the basal surface of DLD-1 cells. Collectively, these results indicate a novel mode of collagen IV deposition in which fibroblasts proximal to epithelial cells exclusively contribute to collagen IV assembly during BM formation.
(キーワード): コラーゲン (collagen) / 細胞外マトリックス (extracellular matrix) / 共培養 / 腸管上皮 / 線維芽細胞
(徳島大学機関リポジトリ): ● Metadata: 117543
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/febs.16559
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35730982; ● Search Scopus @ Elsevier (PMID): 35730982; ● Search Scopus @ Elsevier (DOI): 10.1111/febs.16559

(徳島大学機関リポジトリ: 117543, DOI: 10.1111/febs.16559, PubMed: 35730982) Ryosuke Nishimura, kagayaki Kato, M Saida, Y Kamei, M Takeda, H Miyoshi, Yutaka Yamagata, Yu Amano and Shigenobu Yonemura :
Appropriate tension sensitivity of α-catenin ensures rounding morphogenesis of epithelial spheroids.,
Cell Structure and Function, Vol.47, No.2, 55-73, 2022.

(要約): The adherens junction (AJ) is an actin filament-anchoring junction. It plays a central role in epithelial morphogenesis through cadherin-based recognition and adhesion among cells. The stability and plasticity of AJs are required for the morphogenesis. An actin-binding α-catenin is an essential component of the cadherin-catenin complex and functions as a tension transducer that changes its conformation and induces AJ development in response to tension. Despite much progress in understanding molecular mechanisms of tension sensitivity of α-catenin, its significance on epithelial morphogenesis is still unknown. Here we show that the tension sensitivity of α-catenin is essential for epithelial cells to form round spheroids through proper multicellular rearrangement. Using a novel in vitro suspension culture model, we found that epithelial cells form round spheroids even from rectangular-shaped cell masses with high aspect ratios without using high tension and that increased tension sensitivity of α-catenin affected this morphogenesis. Analyses of AJ formation and cellular tracking during rounding morphogenesis showed cellular rearrangement, probably through AJ remodeling. The rearrangement occurs at the cell mass level, but not single-cell level. Hypersensitive α-catenin mutant-expressing cells did not show cellular rearrangement at the cell mass level, suggesting that the appropriate tension sensitivity of α-catenin is crucial for the coordinated round morphogenesis.Key words: α-catenin, vinculin, adherens junction, morphogenesis, mechanotransduction.
(キーワード): Adherens Junctions / Cadherins / Mechanotransduction, Cellular / Morphogenesis / alpha Catenin
(徳島大学機関リポジトリ): ● Metadata: 117376
(出版サイトへのリンク): ● Publication site (DOI): 10.1247/csf.22014
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35732428; ● Search Scopus @ Elsevier (PMID): 35732428; ● Search Scopus @ Elsevier (DOI): 10.1247/csf.22014

(徳島大学機関リポジトリ: 117376, DOI: 10.1247/csf.22014, PubMed: 35732428) M Mori, T Yao, T Mishina, H Endoh, M Tanaka, N Yonezawa, Y Shimamoto, Shigenobu Yonemura, K Yamagata, TS Kitajima and M Ikawa :
RanGTP and the actin cytoskeleton keep paternal and maternal chromosomes apart during fertilization.,
The Journal of Cell Biology, Vol.220, No.10, 2021.

(要約): Zygotes require two accurate sets of parental chromosomes, one each from the mother and the father, to undergo normal embryogenesis. However, upon egg-sperm fusion in vertebrates, the zygote has three sets of chromosomes, one from the sperm and two from the egg. The zygote therefore eliminates one set of maternal chromosomes (but not the paternal chromosomes) into the polar body through meiosis, but how the paternal chromosomes are protected from maternal meiosis has been unclear. Here we report that RanGTP and F-actin dynamics prevent egg-sperm fusion in proximity to maternal chromosomes. RanGTP prevents the localization of Juno and CD9, egg membrane proteins that mediate sperm fusion, at the cell surface in proximity to maternal chromosomes. Following egg-sperm fusion, F-actin keeps paternal chromosomes away from maternal chromosomes. Disruption of these mechanisms causes the elimination of paternal chromosomes during maternal meiosis. This study reveals a novel critical mechanism that prevents aneuploidy in zygotes.
(キーワード): Actin Cytoskeleton / Animals / Cells, Cultured / Chromosomes / Female / Fertilization / Humans / Mice / Mice, Inbred Strains / ran GTP-Binding Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1083/jcb.202012001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34424312; ● Search Scopus @ Elsevier (PMID): 34424312; ● Search Scopus @ Elsevier (DOI): 10.1083/jcb.202012001

(DOI: 10.1083/jcb.202012001, PubMed: 34424312) Hiroko Saito, F Matsukawa-Usami, T Fujimori, T Kimura, T Ide, T Yamamoto, T Shibata, Kenta Onoue, Satoko Okayama, Shigenobu Yonemura, Kazuyo Misaki, Y Soba, Y Kakui, M Sato, M Toya and Masatoshi Takeichi :
Tracheal motile cilia in mice require CAMSAP3 for the formation of central microtubule pair and coordinated beating.,
Molecular Biology of the Cell, Vol.32, No.20, ar12, 2021.

(要約): Motile cilia of multiciliated epithelial cells undergo synchronized beating to produce fluid flow along the luminal surface of various organs. Each motile cilium consists of an axoneme and a basal body (BB), which are linked by a "transition zone" (TZ). The axoneme exhibits a characteristic 9+2 microtubule arrangement important for ciliary motion, but how this microtubule system is generated is not yet fully understood. Here we show that calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), a protein that can stabilize the minus-end of a microtubule, concentrates at multiple sites of the cilium-BB complex, including the upper region of the TZ or the axonemal basal plate (BP) where the central pair of microtubules (CP) initiates. CAMSAP3 dysfunction resulted in loss of the CP and partial distortion of the BP, as well as the failure of multicilia to undergo synchronized beating. These findings suggest that CAMSAP3 plays pivotal roles in the formation or stabilization of the CP by localizing at the basal region of the axoneme and thereby supports the coordinated motion of multicilia in airway epithelial cells.
(キーワード): Actin Cytoskeleton / Animals / Axoneme / Basal Bodies / Cilia / Epithelial Cells / Female / Male / Mice / Mice, Inbred ICR / Mice, Transgenic / Microtubule-Associated Proteins / Microtubules / Movement / Trachea
(出版サイトへのリンク): ● Publication site (DOI): 10.1091/mbc.E21-06-0303
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34319756; ● Search Scopus @ Elsevier (PMID): 34319756; ● Search Scopus @ Elsevier (DOI): 10.1091/mbc.E21-06-0303

(DOI: 10.1091/mbc.E21-06-0303, PubMed: 34319756) Shotaro Sakakibara, Kiyohito Mizutani, Ayumu Sugiura, Ayuko Sakane, Takuya Sasaki, Shigenobu Yonemura and Yoshimi Takai :
Afadin regulates actomyosin organization through αE-catenin at adherens junctions.,
The Journal of Cell Biology, Vol.219, No.5, 2020.

(要約): Actomyosin-undercoated adherens junctions are critical for epithelial cell integrity and remodeling. Actomyosin associates with adherens junctions through αE-catenin complexed with β-catenin and E-cadherin in vivo; however, in vitro biochemical studies in solution showed that αE-catenin complexed with β-catenin binds to F-actin less efficiently than αE-catenin that is not complexed with β-catenin. Although a "catch-bond model" partly explains this inconsistency, the mechanism for this inconsistency between the in vivo and in vitro results remains elusive. We herein demonstrate that afadin binds to αE-catenin complexed with β-catenin and enhances its F-actin-binding activity in a novel mechanism, eventually inducing the proper actomyosin organization through αE-catenin complexed with β-catenin and E-cadherin at adherens junctions.
(徳島大学機関リポジトリ): ● Metadata: 115835
(出版サイトへのリンク): ● Publication site (DOI): 10.1083/jcb.201907079
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32227204; ● Search Scopus @ Elsevier (PMID): 32227204; ● Search Scopus @ Elsevier (DOI): 10.1083/jcb.201907079

(徳島大学機関リポジトリ: 115835, DOI: 10.1083/jcb.201907079, PubMed: 32227204) S Konishi, T Yano, H Tanaka, T Mizuno, H Kanoh, K Tsukita, T Namba, A Tamura, Shigenobu Yonemura, S Gotoh, H Matsumoto, T Hirai and S Tsukita :
Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions.,
Life Science Alliance, Vol.2, No.4, 2019.

(要約): The paracellular barrier function of tight junctions (TJs) in epithelial cell sheets is robustly maintained against mechanical fluctuations, by molecular mechanisms that are poorly understood. Vinculin is an adaptor of a mechanosensory complex at the adherens junction. Here, we generated vinculin KO Eph4 epithelial cells and analyzed their confluent cell-sheet properties. We found that vinculin is dispensable for the basic TJ structural integrity and the paracellular barrier function for larger solutes. However, vinculin is indispensable for the paracellular barrier function for ions. In addition, TJs stochastically showed dynamically distorted patterns in vinculin KO cell sheets. These KO phenotypes were rescued by transfecting full-length vinculin and by relaxing the actomyosin tension with blebbistatin, a myosin II ATPase activity inhibitor. Our findings indicate that vinculin resists mechanical fluctuations to maintain the TJ paracellular barrier function for ions in epithelial cell sheets.
(キーワード): Actomyosin / Cell Line / Epithelial Cells / Gene Knockout Techniques / HEK293 Cells / Heterocyclic Compounds, 4 or More Rings / Humans / Ions / Stochastic Processes / Tight Junctions / Vinculin
(徳島大学機関リポジトリ): ● Metadata: 116220
(出版サイトへのリンク): ● Publication site (DOI): 10.26508/lsa.201900414
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31399484; ● Search Scopus @ Elsevier (PMID): 31399484; ● Search Scopus @ Elsevier (DOI): 10.26508/lsa.201900414

(徳島大学機関リポジトリ: 116220, DOI: 10.26508/lsa.201900414, PubMed: 31399484) Toshiya Ando, Sayaka Sekine, Sachi Inagaki, Kazuyo Misaki, Laurent Badel, Hiroyuki Moriya, Mustafa M. Sami, Yuki Itakura, Takahiro Chihara, Hokto Kazama, Shigenobu Yonemura and Shigeo Hayashi :
Nanopore Formation in the Cuticle of an Insect Olfactory Sensillum.,
Current Biology, Vol.29, No.9, 1512-1520.e6, 2019.

(要約): Nanometer-level patterned surface structures form the basis of biological functions, including superhydrophobicity, structural coloration, and light absorption [1-3]. In insects, the cuticle overlying the olfactory sensilla has multiple small (50- to 200-nm diameter) pores [4-8], which are supposed to function as a filter that admits odorant molecules, while preventing the entry of larger airborne particles and limiting water loss. However, the cellular processes underlying the patterning of extracellular matrices into functional nano-structures remain unknown. Here, we show that cuticular nanopores in Drosophila olfactory sensilla originate from a curved ultrathin film that is formed in the outermost envelope layer of the cuticle and secreted from specialized protrusions in the plasma membrane of the hair forming (trichogen) cell. The envelope curvature coincides with plasma membrane undulations associated with endocytic structures. The gore-tex/Osiris23 gene encodes an endosomal protein that is essential for envelope curvature, nanopore formation, and odor receptivity and is expressed specifically in developing olfactory trichogen cells. The 24-member Osiris gene family is expressed in cuticle-secreting cells and is found only in insect genomes. These results reveal an essential requirement for nanopores for odor reception and identify Osiris genes as a platform for investigating the evolution of surface nano-fabrication in insects.
(キーワード): Animals / Drosophila melanogaster / Female / Microscopy, Electron, Transmission / Nanopores / Sensilla
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.cub.2019.03.043
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31006566; ● Search Scopus @ Elsevier (PMID): 31006566; ● Search Scopus @ Elsevier (DOI): 10.1016/j.cub.2019.03.043

(DOI: 10.1016/j.cub.2019.03.043, PubMed: 31006566) Sayaka Wakayama, Taiyu Ito, Yuko Kamada, Shigenobu Yonemura, Masatoshi Oosa, Satoshi Kishigami and Teruhiko Wakayama :
Tolerance of the freeze-dried mouse sperm nucleus to temperatures ranging from -196°C to 150°C.,
Scientific Reports, Vol.9, No.1, 5719, 2019.

(要約): It has long been believed that tolerance against extreme environments is possible only for 'lower' groups, such as archaea, bacteria or tardigrades, and not for more 'advanced' species. Here, we demonstrated that the mammalian sperm nucleus also exhibited strong tolerance to cold and hot temperatures. When mouse spermatozoa were freeze-dried (FD), similar to the anhydrobiosis of Tardigrades, all spermatozoa were ostensibly dead after rehydration. However, offspring were obtained from recovered FD sperm nuclei, even after repeated treatment with conditions from liquid nitrogen to room temperature. Conversely, when FD spermatozoa were heated at 95 °C, although the birth rate was decreased with increasing duration of the treatment, offspring were obtained even for FD spermatozoa that had been heat-treated for 2 h. This period was improved up to 6 h when glucose was replaced with trehalose in the freeze-drying medium, and the resistance temperature was extended up to 150 °C for short periods of treatment. Randomly selected offspring grew into healthy adults. Our results suggest that, when considering the sperm nucleus/DNA as the material that is used as a blueprint of life, rather than cell viability, a significant tolerance to extreme temperatures is present even in 'higher' species, such as mammals.
(徳島大学機関リポジトリ): ● Metadata: 114947
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-019-42062-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30952922; ● Search Scopus @ Elsevier (PMID): 30952922; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-019-42062-8

(徳島大学機関リポジトリ: 114947, DOI: 10.1038/s41598-019-42062-8, PubMed: 30952922) Masatsune Tsujioka, Taro QP Uyeda, Yoshiaki Iwadate, Hitesh Patel, Keitaro Shibata, Tenji Yumoto and Shigenobu Yonemura :
Actin-binding domains mediate the distinct distribution of two Dictyostelium Talins through different affinities to specific subsets of actin filaments during directed cell migration.,
PLoS ONE, Vol.14, No.4, e0214736, 2019.

(要約): Although the distinct distribution of certain molecules along the anterior or posterior edge is essential for directed cell migration, the mechanisms to maintain asymmetric protein localization have not yet been fully elucidated. Here, we studied a mechanism for the distinct localizations of two Dictyostelium talin homologues, talin A and talin B, both of which play important roles in cell migration and adhesion. Using GFP fusion, we found that talin B, as well as its C-terminal actin-binding region, which consists of an I/LWEQ domain and a villin headpiece domain, was restricted to the leading edge of migrating cells. This is in sharp contrast to talin A and its C-terminal actin-binding domain, which co-localized with myosin II along the cell posterior cortex, as reported previously. Intriguingly, even in myosin II-null cells, talin A and its actin-binding domain displayed a specific distribution, co-localizing with stretched actin filaments. In contrast, talin B was excluded from regions rich in stretched actin filaments, although a certain amount of its actin-binding region alone was present in those areas. When cells were sucked by a micro-pipette, talin B was not detected in the retracting aspirated lobe where acto-myosin, talin A, and the actin-binding regions of talin A and talin B accumulated. Based on these results, we suggest that talin A predominantly interacts with actin filaments stretched by myosin II through its C-terminal actin-binding region, while the actin-binding region of talin B does not make such distinctions. Furthermore, talin B appears to have an additional, unidentified mechanism that excludes it from the region rich in stretched actin filaments. We propose that these actin-binding properties play important roles in the anterior and posterior enrichment of talin B and talin A, respectively, during directed cell migration.
(徳島大学機関リポジトリ): ● Metadata: 114343
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0214736
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30946777; ● Summary page in Scopus @ Elsevier: 2-s2.0-85063968594

(徳島大学機関リポジトリ: 114343, DOI: 10.1371/journal.pone.0214736, PubMed: 30946777, Elsevier: Scopus) Takuma Shinozuka, Ritsuko Takada, Chosei Yoshida, Shigenobu Yonemura and Shinji Takada :
Wnt produced by stretched roof-plate cells is required for the promotion of cell proliferation around the central canal of the spinal cord,
Development, Vol.146, No.2, dev159343, 2019.

(要約): Cell morphology changes dynamically during embryogenesis, and these changes create new interactions with surrounding cells, some of which are presumably mediated by intercellular signaling. However, the effects of morphological changes on intercellular signaling remain to be fully elucidated. In this study, we examined the effect of morphological changes in Wnt-producing cells on intercellular signaling in the spinal cord. After mid-gestation, roof-plate cells stretched along the dorsoventral axis in the mouse spinal cord, resulting in new contact at their tips with the ependymal cells that surround the central canal. Wnt1 and Wnt3a were produced by the stretched roof-plate cells and delivered to the cell process tip. Whereas Wnt signaling was activated in developing ependymal cells, Wnt activation in dorsal ependymal cells, which were close to the stretched roof plate, was significantly suppressed in embryos with roof plate-specific conditional knockout of , which encodes a factor that is essential for Wnt secretion. Furthermore, proliferation of these cells was impaired in conditional knockout mice during development and after induced spinal cord injury in adults. Therefore, morphological changes in Wnt-producing cells appear to generate new Wnt signal targets.
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/dev.159343
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30651295; ● Search Scopus @ Elsevier (PMID): 30651295; ● Search Scopus @ Elsevier (DOI): 10.1242/dev.159343

(DOI: 10.1242/dev.159343, PubMed: 30651295) Noboru Ishiyama, Rifu Sarpal, Megan N. Wood, Samantha K Garrick, Tadateru Nishikawa, Hanako Hayashi, Anna B Kobb, Annette S. Flozak, Alex Yemelyanov, Rodrigo Fernandez-Gonzalez, Shigenobu Yonemura, Deborah E. Neckband, Cara J. Gottardi, Ulrich Tepass and Mitsuhiko Ikura :
Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions,
Nature Communications, Vol.9, No.1, 5121, 2018.

(要約): α-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which α-catenin engages F-actin under tension remained elusive. Here we show that the α1-helix of the α-catenin actin-binding domain (αcat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length α-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that α1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of αcat-ABD-H1 homodimer suggest that α-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of αcat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.
(キーワード): Actin Cytoskeleton / Actins / Adherens Junctions / Animals / Cadherins / Humans / Protein Structure, Secondary / alpha Catenin
(徳島大学機関リポジトリ): ● Metadata: 114825
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41467-018-07481-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30504777; ● Search Scopus @ Elsevier (PMID): 30504777; ● Search Scopus @ Elsevier (DOI): 10.1038/s41467-018-07481-7

(徳島大学機関リポジトリ: 114825, DOI: 10.1038/s41467-018-07481-7, PubMed: 30504777) Chun-Chun Cheng, Ko Tsutsui, Toru Taguchi, Noriko Sansen, Asako Nakagawa, Kisa Kakiguchi, Shigenobu Yonemura, Chiharu Tanegashima, Sean D Keeley, Hiroshi Kiyonari, Yasuhide Furuta, Yasuko Tomono, Fiona M Watt and Hironobu Fujiwara :
Hair follicle epidermal stem cells define a niche for tactile sensation,
eLife, Vol.7, e38883, 2018.

(要約): The heterogeneity and compartmentalization of stem cells is a common principle in many epithelia, and is known to function in epithelial maintenance, but its other physiological roles remain elusive. Here we show transcriptional and anatomical contributions of compartmentalized epidermal stem cells in tactile sensory unit formation in the mouse hair follicle. Epidermal stem cells in the follicle upper-bulge, where mechanosensory lanceolate complexes innervate, express a unique set of extracellular matrix (ECM) and neurogenesis-related genes. These epidermal stem cells deposit an ECM protein called EGFL6 into the collar matrix, a novel ECM that tightly ensheathes lanceolate complexes. EGFL6 is required for the proper patterning, touch responses, and αv integrin-enrichment of lanceolate complexes. By maintaining a quiescent original epidermal stem cell niche, the old bulge, epidermal stem cells provide anatomically stable follicle-lanceolate complex interfaces, irrespective of the stage of follicle regeneration cycle. Thus, compartmentalized epidermal stem cells provide a niche linking the hair follicle and the nervous system throughout the hair cycle.
(キーワード): Animals / Axons / Cell Adhesion / Epidermal Cells / Extracellular Matrix / Extracellular Matrix Proteins / Gene Expression Regulation / Glycoproteins / Hair Follicle / Integrin alphaV / Mice, Knockout / Neoplasm Proteins / Neurons / Peptides / Schwann Cells / Stem Cell Niche / Stem Cells / Touch
(徳島大学機関リポジトリ): ● Metadata: 115091
(出版サイトへのリンク): ● Publication site (DOI): 10.7554/eLife.38883
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30355452; ● Summary page in Scopus @ Elsevier: 2-s2.0-85056407580

(徳島大学機関リポジトリ: 115091, DOI: 10.7554/eLife.38883, PubMed: 30355452, Elsevier: Scopus) Akira Honda, Tomoko Kita, Shri Vidhya Seshadri, Kazuyo Misaki, Jamal Ahmed, John E. Ladbury, Guy P. Richardson, Shigenobu Yonemura and Raj K. Lather :
FGFR1-mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.,
Proceedings of the National Academy of Sciences of the United States of America, Vol.115, No.33, 8388-8393, 2018.

(要約): The mechanosensory hair cells of the inner ear are required for hearing and balance and have a distinctive apical structure, the hair bundle, that converts mechanical stimuli into electrical signals. This structure comprises a single cilium, the kinocilium, lying adjacent to an ensemble of actin-based projections known as stereocilia. Hair bundle polarity depends on kinociliary protocadherin-15 (Pcdh15) localization. Protocadherin-15 is found only in hair-cell kinocilia, and is not localized to the primary cilia of adjacent supporting cells. Thus, Pcdh15 must be specifically targeted and trafficked into the hair-cell kinocilium. Here we show that kinocilial Pcdh15 trafficking relies on cell type-specific coupling to the generic intraflagellar transport (IFT) transport mechanism. We uncover a role for fibroblast growth factor receptor 1 (FGFR1) in loading Pcdh15 onto kinociliary transport particles in hair cells. We find that on activation, FGFR1 binds and phosphorylates Pcdh15. Moreover, we find a previously uncharacterized role for clathrin in coupling this kinocilia-specific cargo with the anterograde IFT-B complex through the adaptor, DAB2. Our results identify a modified ciliary transport pathway used for Pcdh15 transport into the cilium of the inner ear hair cell and coordinated by FGFR1 activity.
(キーワード): Adaptor Proteins, Vesicular Transport / Animals / Cadherins / Chick Embryo / Clathrin / Flagella / Hair Cells, Auditory, Inner / Mice / Phosphorylation / Protein Precursors / Protein Transport / Receptor, Fibroblast Growth Factor, Type 1
(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.1719861115
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30061390; ● Search Scopus @ Elsevier (PMID): 30061390; ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.1719861115

(DOI: 10.1073/pnas.1719861115, PubMed: 30061390) So Goto, Akishi Onishi, Kazuyo Misaki, Shigenobu Yonemura, Sunao Sugita, Hiromi Ito, Yoko Ohigashi, Masatsugu Ema, Hirokazu Sakaguchi, Kohl Nishida and Masayo Takahashi :
Neural retina-specific Aldh1a1 controls dorsal choroidal vascular development via Sox9 expression in retinal pigment epithelial cells,
eLife, Vol.7, 2018.

(要約): VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of mice and RPE-specific disruption of Sox9 phenocopied choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion.
(キーワード): Aldehyde Dehydrogenase / Animals / Choroid / Epithelial Cells / Gene Expression Regulation / Mice, Inbred C57BL / Mice, Knockout / Neovascularization, Physiologic / Retinal Pigment Epithelium / SOX9 Transcription Factor / Tretinoin / Vascular Endothelial Growth Factor A
(出版サイトへのリンク): ● Publication site (DOI): 10.7554/eLife.32358
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29609731; ● Summary page in Scopus @ Elsevier: 2-s2.0-85051983205

(DOI: 10.7554/eLife.32358, PubMed: 29609731, Elsevier: Scopus) Yoshinori Hirano, Yu Amano, Shigenobu Yonemura and Toshio Takoshima :
The force-sensing device region of alpha-catenin in an intrinsically disordered segment in the absence of intramolecular stabilization of the auto inhibitory form.,
Genes to Cells, Vol.23, No.5, 370-385, 2018.

(要約): Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G. Our molecular dissection study showed that helix bundles F and G are stable in solution in each isolated form, whereas helix bundle E that contains VBS1 is unstable and intrinsically disordered in solution in the isolated form. We successfully identified key residues mediating the autoinhibition and produced mutated α-catenins that display variable force sensitivity and autoinhibition. Using these mutants, we demonstrate both in vitro and in vivo that, in the absence of this stabilization, the helix bundle containing VBS1 would adopt an unfolded form, thus exposing VBS for vinculin binding. We provide evidence for importance of mechanotransduction with the intrinsic force sensitivity for vinculin recruitment to adherens junctions of epithelial cell sheets with mutated α-catenins.
(キーワード): Actins / Adherens Junctions / Animals / Binding Sites / Crystallography, X-Ray / Mechanotransduction, Cellular / Mice / Models, Molecular / Mutation / Protein Binding / Protein Conformation / Protein Folding / Vinculin / alpha Catenin
(出版サイトへのリンク): ● Publication site (DOI): 10.1111/gtc.12578
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29542234; ● Search Scopus @ Elsevier (PMID): 29542234; ● Search Scopus @ Elsevier (DOI): 10.1111/gtc.12578

(DOI: 10.1111/gtc.12578, PubMed: 29542234) Satoshi Iraha, Hung-Ya Tu, Suguru Yamasaki, Takahiro Kagawa, Motohito Goto, Riichi Takahashi, Takehito Watanabe, Sunao Sugita, Shigenobu Yonemura, Genshiro A. Sunagawa, Take Matsuyama, Momo Fujii, Atsushi Kuwahara, Akiyoshi Kishino, Nosh Koide, Mototsugu Eiraku, Hidenobu Tanihara, Masayo Takahashi and Michiko Mandai :
Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation,
Stem Cell Reports, Vol.10, No.3, 1059-1074, 2018.

(要約): Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets.
(キーワード): Animals / Disease Models, Animal / Embryonic Stem Cells / Female / Humans / Induced Pluripotent Stem Cells / Male / Mice / Mice, Inbred C57BL / Mice, Inbred NOD / Mice, Transgenic / Photoreceptor Cells / Retina / Retinal Degeneration / Stem Cell Transplantation
(徳島大学機関リポジトリ): ● Metadata: 115734
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.stemcr.2018.01.032
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29503091; ● Search Scopus @ Elsevier (PMID): 29503091; ● Search Scopus @ Elsevier (DOI): 10.1016/j.stemcr.2018.01.032

(徳島大学機関リポジトリ: 115734, DOI: 10.1016/j.stemcr.2018.01.032, PubMed: 29503091) koichiro Maki, Sung-Woong Han, Yoshinori Hirano, Shigenobu Yonemura, Toshio Takoshima and Taiji Adachi :
Real-time TIRF observation of vinculin recruitment to stretched alpha-catenin by AFM,
Scientific Reports, Vol.8, No.1, 1575, 2018.

(要約): Adherens junctions (AJs) adaptively change their intensities in response to intercellular tension; therefore, they integrate tension generated by individual cells to drive multicellular dynamics, such as morphogenetic change in embryos. Under intercellular tension, α-catenin, which is a component protein of AJs, acts as a mechano-chemical transducer to recruit vinculin to promote actin remodeling. Although in vivo and in vitro studies have suggested that α-catenin-mediated mechanotransduction is a dynamic molecular process, which involves a conformational change of α-catenin under tension to expose a cryptic vinculin binding site, there are no suitable experimental methods to directly explore the process. Therefore, in this study, we developed a novel system by combining atomic force microscopy (AFM) and total internal reflection fluorescence (TIRF). In this system, α-catenin molecules (residues 276-634; the mechano-sensitive M-M domain), modified on coverslips, were stretched by AFM and their recruitment of Alexa-labeled full-length vinculin molecules, dissolved in solution, were observed simultaneously, in real time, using TIRF. We applied a physiologically possible range of tensions and extensions to α-catenin and directly observed its vinculin recruitment. Our new system could be used in the fields of mechanobiology and biophysics to explore functions of proteins under tension by coupling biomechanical and biochemical information.
(キーワード): Animals / Fluorometry / Mice / Microscopy, Atomic Force / Protein Binding / Vinculin / alpha Catenin
(徳島大学機関リポジトリ): ● Metadata: 114956
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-018-20115-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29371682; ● Search Scopus @ Elsevier (PMID): 29371682; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-018-20115-8

(徳島大学機関リポジトリ: 114956, DOI: 10.1038/s41598-018-20115-8, PubMed: 29371682) Toshihiro Akiyama, Akihito Inoko, Yuichi Kaji, Shigenobu Yonemura, Kisa Kakiguchi, Hiroki Segawa, Kei Ishitsuka, Masaki Yoshida, Osamu Numata, Philippe Leproux, Vincent Couderc, Tetsuro Oshika and Hideaki Kano :
SHG-specificity of cellular Rootletin filaments enables naïve imaging with universal conservation.,
Scientific Reports, Vol.7, 39967, 2017.

(要約): Despite growing demand for truly naïve imaging, label-free observation of cilium-related structure remains challenging, and validation of the pertinent molecules is correspondingly difficult. In this study, in retinas and cultured cells, we distinctively visualized Rootletin filaments in rootlets in the second harmonic generation (SHG) channel, integrated in custom coherent nonlinear optical microscopy (CNOM) with a simple, compact, and ultra-broadband supercontinuum light source. This SHG signal was primarily detected on rootlets of connecting cilia in the retinal photoreceptor and was validated by colocalization with anti-Rootletin staining. Transfection of cells with Rootletin fragments revealed that the SHG signal can be ascribed to filaments assembled from the R234 domain, but not to cross-striations assembled from the R123 domain. Consistent with this, Rootletin-depleted cells lacked SHG signal expected as centrosome linker. As a proof of concept, we confirmed that similar fibrous SHG was observed even in unicellular ciliates. These findings have potential for broad applications in clinical diagnosis and biophysical experiments with various organisms.
(徳島大学機関リポジトリ): ● Metadata: 112380
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/srep39967
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28059168; ● Search Scopus @ Elsevier (PMID): 28059168; ● Search Scopus @ Elsevier (DOI): 10.1038/srep39967

(徳島大学機関リポジトリ: 112380, DOI: 10.1038/srep39967, PubMed: 28059168) T Otani, Y Ogura, K Misaki, T Maeda, A Kimpara, S Yonemura, S. Hayashi and Shigenobu Yonemura :
IKK inhibits PKC to promote Fascin-dependent actin bundling.,
Development, Vol.143, No.20, 3806-3816, 2016.

(要約): Signaling molecules have pleiotropic functions and are activated by various extracellular stimuli. Protein kinase C (PKC) is activated by diverse receptors, and its dysregulation is associated with diseases including cancer. However, how the undesired activation of PKC is prevented during development remains poorly understood. We have previously shown that a protein kinase, IKKϵ, is active at the growing bristle tip and regulates actin bundle organization during Drosophila bristle morphogenesis. Here, we demonstrate that IKKϵ regulates the actin bundle localization of a dynamic actin cross-linker, Fascin. IKKϵ inhibits PKC, thereby protecting Fascin from inhibitory phosphorylation. Excess PKC activation is responsible for the actin bundle defects in IKKϵ-deficient bristles, whereas PKC is dispensable for bristle morphogenesis in wild-type bristles, indicating that PKC is repressed by IKKϵ in wild-type bristle cells. These results suggest that IKKϵ prevents excess activation of PKC during bristle morphogenesis.
(キーワード): Actins / Animals / Carrier Proteins / Drosophila / Drosophila Proteins / I-kappa B Kinase / Microfilament Proteins / Phosphorylation / Protein Kinase C / Signal Transduction
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/dev.138495
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27578797; ● Search Scopus @ Elsevier (PMID): 27578797; ● Search Scopus @ Elsevier (DOI): 10.1242/dev.138495

(DOI: 10.1242/dev.138495, PubMed: 27578797) M Yoshida, E Kajikawa, D Yamamoto, D Kurokawa, S Yonemura, K Kobayashi, H Kiyonari, S. Aizawa and Shigenobu Yonemura :
Conserved and Divergent Expression Patterns of Markers of Axial Development in the laboratory opossum, Monodelphis domestica.,
Developmental Dynamics, Vol.245, No.12, 1176-1188, 2016.

(要約): Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short-tailed opossum, a metatherian. Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post-coitus. Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176-1188, 2016. © 2016 Wiley Periodicals, Inc.
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/dvdy.24459
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27666927; ● Search Scopus @ Elsevier (PMID): 27666927; ● Search Scopus @ Elsevier (DOI): 10.1002/dvdy.24459

(DOI: 10.1002/dvdy.24459, PubMed: 27666927) Y Iwasaki, S Sugita, M Mandai, S Yonemura, A Onishi, S Ito, M Mochizuki, K Ohno-Matsui, M. Takahashi and Shigenobu Yonemura :
Differentiation/Purification Protocol for Retinal Pigment Epithelium from Mouse Induced Pluripotent Stem Cells as a Research Tool.,
PLoS ONE, Vol.11, No.7, e0158282, 2016.

(要約): To establish a novel protocol for differentiation of retinal pigment epithelium (RPE) with high purity from mouse induced pluripotent stem cells (iPSC). Retinal progenitor cells were differentiated from mouse iPSC, and RPE differentiation was then enhanced by activation of the Wnt signaling pathway, inhibition of the fibroblast growth factor signaling pathway, and inhibition of the Rho-associated, coiled-coil containing protein kinase signaling pathway. Expanded pigmented cells were purified by plate adhesion after Accutase® treatment. Enriched cells were cultured until they developed a cobblestone appearance with cuboidal shape. The characteristics of iPS-RPE were confirmed by gene expression, immunocytochemistry, and electron microscopy. Functions and immunologic features of the iPS-RPE were also evaluated. We obtained iPS-RPE at high purity (approximately 98%). The iPS-RPE showed apical-basal polarity and cellular structure characteristic of RPE. Expression levels of several RPE markers were lower than those of freshly isolated mouse RPE but comparable to those of primary cultured RPE. The iPS-RPE could form tight junctions, phagocytose photoreceptor outer segments, express immune antigens, and suppress lymphocyte proliferation. We successfully developed a differentiation/purification protocol to obtain mouse iPS-RPE. The mouse iPS-RPE can serve as an attractive tool for functional and morphological studies of RPE.
(キーワード): Animals / Cell Communication / Cell Culture Techniques / Cell Differentiation / Cell Proliferation / Cells, Cultured / Collagenases / Embryonic Stem Cells / Induced Pluripotent Stem Cells / Lymphocytes / Mice / Peptide Hydrolases / Phagocytosis / Retinal Pigment Epithelium / Rod Cell Outer Segment / Signal Transduction / rho-Associated Kinases
(徳島大学機関リポジトリ): ● Metadata: 112340
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pone.0158282
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27385038; ● Search Scopus @ Elsevier (PMID): 27385038; ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0158282

(徳島大学機関リポジトリ: 112340, DOI: 10.1371/journal.pone.0158282, PubMed: 27385038) M Yoshida, E Kajikawa, D Kurokawa, M Noro, T Iwai, S Yonemura, K Kobayashi, H Kiyonari, S. Aizawa and Shigenobu Yonemura :
Conserved and Divergent Expression Patterns of Markers of Axial Development in Reptilian Embryos: Chinese Soft-shell Turtle and Madagascar Ground Gecko.,
Developmental Biology, Vol.415, No.1, 122-142, 2016.

(要約): The processes of development leading up to gastrulation have been markedly altered during the evolution of amniotes, and it is uncertain how the mechanisms of axis formation are conserved and diverged between mouse and chick embryos. To assess the conservation and divergence of these mechanisms, this study examined gene expression patterns during the axis formation process in Chinese soft-shell turtle and Madagascar ground gecko preovipositional embryos. The data suggest that NODAL signaling, similarly to avian embryos but in contrast to eutherian embryos, does not have a role in epiblast and hypoblast development in reptilian embryos. The posterior marginal epiblast (PME) is the initial molecular landmark of axis formation in reptilian embryos prior to primitive plate development. Ontogenetically, PME may be the precursor of the primitive plate, and phylogenetically, Koller's sickle and posterior marginal zone in avian development may have been derived from the PME. Most of the genes expressed in the mouse anterior visceral endoderm (AVE genes), especially signaling antagonist genes, are not expressed in the hypoblast of turtle and gecko embryos, though they are expressed in the avian hypoblast. This study proposes that AVE gene expression in the hypoblast and the visceral endoderm could have been independently established in avian and eutherian lineages, similar to the primitive streak that has been independently acquired in these lineages.
(キーワード): Animals / Blastoderm / Body Patterning / Embryo, Nonmammalian / Embryonic Development / Endoderm / Gastrulation / Gene Expression Regulation, Developmental / Homeodomain Proteins / Lizards / Nodal Protein / Phylogeny / Primitive Streak / Species Specificity / Transcription Factors / Turtles
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ydbio.2016.05.005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27174471; ● Search Scopus @ Elsevier (PMID): 27174471; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ydbio.2016.05.005

(DOI: 10.1016/j.ydbio.2016.05.005, PubMed: 27174471) A Onodera, K Yayama, A Tanaka, H Morosawa, T Furuta, N Takeda, K Kakiguchi, S Yonemura, I Yanagihara, Y Tsutsumi, Y. Kawai and Shigenobu Yonemura :
Amorphous nanosilica particles evoke vascular relaxation through PI3K/Akt/eNOS signaling.,
Fundamental & Clinical Pharmacology, Vol.30, No.5, 419-428, 2016.

(出版サイトへのリンク): ● Publication site (DOI): 10.1111/fcp.12206
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1111/fcp.12206

(DOI: 10.1111/fcp.12206) Y Otowa, K Moriwaki, K Sano, M Shirakabe, S Yonemura, M Shibuya, J Rossant, T Suda, Y Kakeji, M. Hirashima and Shigenobu Yonemura :
Flt1/VEGFR1 heterozygosity causes transient embryonic edema.,
Scientific Reports, Vol.6, 27186, 2016.

(要約): Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1(+/-)) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1(+/-) capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1(+/-) embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1(-/-) mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1(+/-); Aspp1(-/-) mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype.
(徳島大学機関リポジトリ): ● Metadata: 112376
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/srep27186
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27251772; ● Search Scopus @ Elsevier (PMID): 27251772; ● Search Scopus @ Elsevier (DOI): 10.1038/srep27186

(徳島大学機関リポジトリ: 112376, DOI: 10.1038/srep27186, PubMed: 27251772) Y Higashiguchi, K Katsuta, T Minegishi, S Yonemura, A Urasaki, N. Inagaki and Shigenobu Yonemura :
Identification of a shootin1 isoform expressed in peripheral tissues.,
Cell and Tissue Research, Vol.366, No.1, 75-87, 2016.

(要約): Shootin1 is a brain-specific cytoplasmic protein involved in neuronal polarity formation and axon outgrowth. It accumulates at the leading edge of axonal growth cones, where it mediates the mechanical coupling between F-actin retrograde flow and cell adhesions as a clutch molecule, thereby producing force for axon outgrowth. In this study, we report a novel splicing isoform of shootin1 which is expressed not only in the brain but also in peripheral tissues. We have renamed the brain-specific shootin1 as shootin1a and termed the novel isoform as shootin1b. Immunoblot and immunohistochemical analyses with a shootin1b-specific antibody revealed that shootin1b is distributed in various mouse tissues including the lung, liver, stomach, intestines, spleen, pancreas, kidney and skin. Interestingly, shootin1b immunoreactivity was widely detected in epithelial cells that constitute simple and stratified epithelia; in some cells, it colocalized with E-cadherin and cortactin at cell-cell contact sites. Shootin1b also localized in dendritic cells in the spleen. These results suggest that shootin1b may function in various peripheral tissues including epithelial cells.
(キーワード): Aging / Amino Acid Sequence / Animals / Antibody Specificity / Cadherins / Cell Communication / Cortactin / Immunohistochemistry / Mice, Inbred C57BL / Nerve Tissue Proteins / Organ Specificity / Protein Isoforms / Protein Transport / Rats / Tissue Distribution
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s00441-016-2415-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27177867; ● Search Scopus @ Elsevier (PMID): 27177867; ● Search Scopus @ Elsevier (DOI): 10.1007/s00441-016-2415-9

(DOI: 10.1007/s00441-016-2415-9, PubMed: 27177867) N Shibata, M Kashima, T Ishiko, O Nishimura, L Rouhana, K Misaki, S Yonemura, K Saito, H Siomi, MC Siomi, K. Agata and Shigenobu Yonemura :
Inheritance of a Nuclear PIWI from Pluripotent Stem Cells by Somatic Descendants Ensures Differentiation by Silencing Transposons in Planarian.,
Developmental Cell, Vol.37, No.3, 226-237, 2016.

(要約): Differentiation of pluripotent stem cells (PSCs) requires transposon silencing throughout the process. PIWIs, best known as key factors in germline transposon silencing, are also known to act in somatic differentiation of planarian PSCs (neoblasts). However, how PIWIs control the latter process remains elusive. Here, using Dugesia japonica, we show that a nuclear PIWI, DjPiwiB, was bound to PIWI-interacting RNAs (generally key mediators of PIWI-dependent transposon silencing), and was detected in not only neoblasts but also their descendant somatic cells, which do not express piwi. In contrast, cytoplasmic DjPiwiA and DjPiwiC were detected only in neoblasts, in accord with their transcription there. DjPiwiB was indispensable for regeneration, but dispensable for transposon silencing in neoblasts. However, transposons were derepressed at the onset of differentiation in DjPiwiB-knockdown planarians. Thus, DjPiwiB appears to be inherited by descendant somatic cells of neoblasts to ensure transposon silencing in those cells, which are unable to produce PIWI proteins.
(キーワード): Animals / Argonaute Proteins / Base Sequence / Cell Differentiation / Cell Nucleus / DNA Transposable Elements / Gene Silencing / Immunohistochemistry / Inheritance Patterns / Models, Biological / Planarians / Pluripotent Stem Cells / RNA, Small Interfering
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.devcel.2016.04.009
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27165555; ● Search Scopus @ Elsevier (PMID): 27165555; ● Search Scopus @ Elsevier (DOI): 10.1016/j.devcel.2016.04.009

(DOI: 10.1016/j.devcel.2016.04.009, PubMed: 27165555) K Maki, SW Han, Y Hirano, S Yonemura, T Hakoshima, T. Adachi and Shigenobu Yonemura :
Mechano-adaptive sensory mechanism of -catenin under tension.,
Scientific Reports, Vol.6, 24878, 2016.

(要約): The contractile forces in individual cells drive the tissue processes, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, α-catenin molecule acts as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, α-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. In this study, we revealed how α-catenin retains its activated state while avoiding unfolding under tension. Using single-molecule force spectroscopy employing atomic force microscopy (AFM), we found that mechanically activated α-catenin fragment had higher mechanical stability than a non-activated fragment. The results of our experiments using mutated and segmented fragments showed that the key intramolecular interactions acted as a conformational switch. We also found that the conformation of α-catenin was reinforced by vinculin binding. We demonstrate that α-catenin adaptively changes its conformation under tension to a stable intermediate state, binds to vinculin, and finally settles into a more stable state reinforced by vinculin binding. Our data suggest that the plastic characteristics of α-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels.
(徳島大学機関リポジトリ): ● Metadata: 112377
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/srep24878
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27109499; ● Search Scopus @ Elsevier (PMID): 27109499; ● Search Scopus @ Elsevier (DOI): 10.1038/srep24878

(徳島大学機関リポジトリ: 112377, DOI: 10.1038/srep24878, PubMed: 27109499) H Inaba, H Goto, K Kasahara, K Kumamoto, Shigenobu Yonemura, A Inoko, S Yamano, H Wanibuchi, D He, N Goshima, T Kiyono, S Hirotsune and M Inagaki :
Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway.,
The Journal of Cell Biology, Vol.212, No.4, 409-423, 2016.

(要約): Primary cilia protrude from the surface of quiescent cells and disassemble at cell cycle reentry. We previously showed that ciliary reassembly is suppressed by trichoplein-mediated Aurora A activation pathway in growing cells. Here, we report that Ndel1, a well-known modulator of dynein activity, localizes at the subdistal appendage of the mother centriole, which nucleates a primary cilium. In the presence of serum, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation, which is reverted by forced trichoplein expression or coknockdown of KCTD17 (an E3 ligase component protein for trichoplein). Serum starvation induced transient Ndel1 degradation, subsequent to the disappearance of trichoplein at the mother centriole. Forced expression of Ndel1 suppressed trichoplein degradation and axonemal microtubule extension during ciliogenesis, similar to trichoplein induction or KCTD17 knockdown. Most importantly, the proportion of ciliated and quiescent cells was increased in the kidney tubular epithelia of newborn Ndel1-hypomorphic mice. Thus, Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / Animals, Newborn / Aurora Kinase A / Carrier Proteins / Cell Cycle Checkpoints / Cell Proliferation / Centrioles / Cilia / Epithelial Cells / Genotype / HeLa Cells / Humans / Kidney Tubules / Mice / Mice, Knockout / Microtubules / Phenotype / Protein Stability / Proteolysis / RNA Interference / Signal Transduction / Swiss 3T3 Cells / Time Factors / Transfection
(出版サイトへのリンク): ● Publication site (DOI): 10.1083/jcb.201507046
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26880200; ● Summary page in Scopus @ Elsevier: 2-s2.0-84959468418

(DOI: 10.1083/jcb.201507046, PubMed: 26880200, Elsevier: Scopus) C Ozone, H Suga, M Eiraku, T Kagoshima, Shigenobu Yonemura, N Takata, Y Oiso, T Tsuji and Y Sasai :
Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.,
Nature Communications, Vol.7, 10351, 2016.

(要約): Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine.
(キーワード): Adrenocorticotropic Hormone / Animals / Cell Culture Techniques / Corticotrophs / Embryonic Development / Embryonic Stem Cells / Growth Hormone / Humans / Hypopituitarism / Mice / Pituitary Gland, Anterior / Tissue Engineering
(徳島大学機関リポジトリ): ● Metadata: 112430
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/ncomms10351
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26762480; ● Summary page in Scopus @ Elsevier: 2-s2.0-84954138949

(徳島大学機関リポジトリ: 112430, DOI: 10.1038/ncomms10351, PubMed: 26762480, Elsevier: Scopus) H Shirai, K Matsushita, A Kuwahara, Shigenobu Yonemura, T Nakano, J Assawachananount, T Kimura, K Saito, H Terasaki, M Eiraku, Y Sarai and Y Takahashi :
Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration.,
Proceedings of the National Academy of Sciences of the United States of America, Vol.113, No.1, E81-E90, 2016.

(要約): Retinal transplantation therapy for retinitis pigmentosa is increasingly of interest due to accumulating evidence of transplantation efficacy from animal studies and development of techniques for the differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells into retinal tissues or cells. In this study, we aimed to assess the potential clinical utility of hESC-derived retinal tissues (hESC-retina) using newly developed primate models of retinal degeneration to obtain preparatory information regarding the potential clinical utility of these hESC-retinas in transplantation therapy. hESC-retinas were first transplanted subretinally into nude rats with or without retinal degeneration to confirm their competency as a graft to mature to form highly specified outer segment structure and to integrate after transplantation. Two focal selective photoreceptor degeneration models were then developed in monkeys by subretinal injection of cobalt chloride or 577-nm optically pumped semiconductor laser photocoagulation. The utility of the developed models and a practicality of visual acuity test developed for monkeys were evaluated. Finally, feasibility of hESC-retina transplantation was assessed in the developed monkey models under practical surgical procedure and postoperational examinations. Grafted hESC-retina was observed differentiating into a range of retinal cell types, including rod and cone photoreceptors that developed structured outer nuclear layers after transplantation. Further, immunohistochemical analyses suggested the formation of host-graft synaptic connections. The findings of this study demonstrate the clinical feasibility of hESC-retina transplantation and provide the practical tools for the optimization of transplantation strategies for future clinical applications.
(キーワード): Animals / Cell Differentiation / Cobalt / Disease Models, Animal / Haplorhini / Human Embryonic Stem Cells / Humans / Photoreceptor Cells / Primates / Rats / Retina / Retinal Degeneration
(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.1512590113
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26699487; ● Summary page in Scopus @ Elsevier: 2-s2.0-84953253310

(DOI: 10.1073/pnas.1512590113, PubMed: 26699487, Elsevier: Scopus) K Shinohara, D Chen, T Nishida, K Misaki, Shigenobu Yonemura and H Hamada :
Absence of Radial Spokes in Mouse Node Cilia Is Required for Rotational Movement but Confers Ultrastructural Instability as a Trade-Off.,
Developmental Cell, Vol.35, No.2, 236-246, 2015.

(要約): Determination of left-right asymmetry in mouse embryos is established by a leftward fluid flow that is generated by clockwise rotation of node cilia. How node cilia achieve stable unidirectional rotation has remained unknown, however. Here we show that brief exposure to the microtubule-stabilizing drug paclitaxel (Taxol) induces randomly directed rotation and changes the ultrastructure of node cilia. In vivo observations and a computer simulation revealed that a regular 9+0 arrangement of doublet microtubules is essential for stable unidirectional rotation of node cilia. The 9+2 motile cilia of the airway, which manifest planar beating, are resistant to Taxol treatment. However, the airway cilia of mice lacking the radial spoke head protein Rsph4a undergo rotational movement instead of planar beating, are prone to microtubule rearrangement, and are sensitive to Taxol. Our results suggest that the absence of radial spokes allows node cilia to rotate unidirectionally but, as a trade-off, renders them ultrastructurally fragile.
(キーワード): Animals / Body Patterning / Cilia / Embryo, Mammalian / Embryonic Development / Mice / Microtubules / Paclitaxel
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.devcel.2015.10.001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26506310; ● Summary page in Scopus @ Elsevier: 2-s2.0-84945124366

(DOI: 10.1016/j.devcel.2015.10.001, PubMed: 26506310, Elsevier: Scopus) M Takeuchi, S Yamaguchi, Shigenobu Yonemura, K Kakiguchi, Y Sato, T Higashiyama, T Shimizu and M Habi :
Type IV Collagen Controls the Axogenesis of Cerebellar Granule Cells by Regulating Basement Membrane Integrity in Zebrafish.,
PLoS Genetics, Vol.11, e1005587, 2015.

(要約): Granule cells (GCs) are the major glutamatergic neurons in the cerebellum, and GC axon formation is an initial step in establishing functional cerebellar circuits. In the zebrafish cerebellum, GCs can be classified into rostromedial and caudolateral groups, according to the locations of their somata in the corresponding cerebellar lobes. The axons of the GCs in the caudolateral lobes terminate on crest cells in the dorsal hindbrain, as well as forming en passant synapses with Purkinje cells in the cerebellum. In the zebrafish mutant shiomaneki, the caudolateral GCs extend aberrant axons. Positional cloning revealed that the shiomaneki (sio) gene locus encodes Col4a6, a subunit of type IV collagen, which, in a complex with Col4a5, is a basement membrane (BM) component. Both col4a5 and col4a6 mutants displayed similar abnormalities in the axogenesis of GCs and retinal ganglion cells (RGCs). Although type IV collagen is reported to control axon targeting by regulating the concentration gradient of an axonal guidance molecule Slit, Slit overexpression did not affect the GC axons. The structure of the BM surrounding the tectum and dorsal hindbrain was disorganized in the col4a5 and col4a6 mutants. Moreover, the abnormal axogenesis of the caudolateral GCs and the RGCs was coupled with aberrant BM structures in the type IV collagen mutants. The regrowth of GC axons after experimental ablation revealed that the original and newly formed axons displayed similar branching and extension abnormalities in the col4a6 mutants. These results collectively suggest that type IV collagen controls GC axon formation by regulating the integrity of the BM, which provides axons with the correct path to their targets.
(キーワード): Animals / Axons / Basement Membrane / Cerebellum / Collagen Type IV / Extracellular Matrix / Nerve Tissue Proteins / Purkinje Cells / Retinal Ganglion Cells / Zebrafish / Zebrafish Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1371/journal.pgen.1005587
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26451951; ● Summary page in Scopus @ Elsevier: 2-s2.0-84946592981

(DOI: 10.1371/journal.pgen.1005587, PubMed: 26451951, Elsevier: Scopus) K Nakanishi, K Kakiguchi, Shigenobu Yonemura, A Nakano and N Morishima :
Transient Ca2+ depletion from the endoplasmic reticulum is critical for skeletal myoblast differentiation.,
The FASEB journal, Vol.29, No.5, 2137-2149, 2015.

(要約): Endoplasmic reticulum (ER) stress is a cellular condition in which unfolded proteins accumulate in the ER because of various but specific causes. Physiologic ER stress occurs transiently during myoblast differentiation, and although its cause remains unknown, it plays a critical role in myofiber formation. To examine the mechanism underlying ER stress, we monitored ER morphology during differentiation of murine myoblasts. Novel ER-derived structures transiently appeared prior to myoblast fusion both in vitro and in vivo. Electron microscopy studies revealed that these structures consisted of pseudoconcentric ER cisternae with narrow lumens. Similar structures specifically formed by pharmacologically induced ER Ca(2+) depletion, and inhibition of ER Ca(2+) efflux channels in differentiating myoblasts considerably suppressed ER-specific deformation and ER stress signaling. Thus, we named the novel structures stress-activated response to Ca(2+) depletion (SARC) bodies. Prior to SARC body formation, stromal interaction molecule 1 (STIM1), an ER Ca(2+) sensor protein, formed ER Ca(2+) depletion-specific clusters. Furthermore, myoblast differentiation manifested by myoblast fusion did not proceed under the same conditions as inhibition of ER Ca(2+) depletion. Altogether, these observations suggest that ER Ca(2+) depletion is a prerequisite for myoblast fusion, causing both physiologic ER stress signaling and SARC body formation.
(キーワード): Animals / Blotting, Western / Calcium / Calcium Channels / Cell Differentiation / Cell Membrane / Cells, Cultured / Endoplasmic Reticulum / Endoplasmic Reticulum Stress / Immunoenzyme Techniques / Mice / Myoblasts, Skeletal / Signal Transduction
(出版サイトへのリンク): ● Publication site (DOI): 10.1096/fj.14-261529
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25678623; ● Search Scopus @ Elsevier (PMID): 25678623; ● Search Scopus @ Elsevier (DOI): 10.1096/fj.14-261529

(DOI: 10.1096/fj.14-261529, PubMed: 25678623) H Nagai, M Sezaki, K Kakiguchi, Y Nakaya, HC Lee, R Lather, T Sasanami, JK Han, Shigenobu Yonemura and G Sheng :
Cellular analysis of cleavage-stage chick embryos reveals hidden conservation in vertebrate early development.,
Development, Vol.142, No.7, 1279-1286, 2015.

(要約): Birds and mammals, phylogenetically close amniotes with similar post-gastrula development, exhibit little conservation in their post-fertilization cleavage patterns. Data from the mouse suggest that cellular morphogenesis and molecular signaling at the cleavage stage play important roles in lineage specification at later (blastula and gastrula) stages. Very little is known, however, about cleavage-stage chick embryos, owing to their poor accessibility. This period of chick development takes place before egg-laying and encompasses several fundamental processes of avian embryology, including zygotic gene activation (ZGA) and blastoderm cell-layer increase. We have carried out morphological and cellular analyses of cleavage-stage chick embryos covering the first half of pre-ovipositional development, from Eyal-Giladi and Kochav stage (EGK-) I to EGK-V. Scanning electron microscopy revealed remarkable subcellular details of blastomere cellularization and subgerminal cavity formation. Phosphorylated RNA polymerase II immunostaining showed that ZGA in the chick starts at early EGK-III during the 7th to 8th nuclear division cycle, comparable with the time reported for other yolk-rich vertebrates (e.g. zebrafish and Xenopus). The increase in the number of cell layers after EGK-III is not a direct consequence of oriented cell division. Finally, we present evidence that, as in the zebrafish embryo, a yolk syncytial layer is formed in the avian embryo after EGK-V. Our data suggest that several fundamental features of cleavage-stage development in birds resemble those in yolk-rich anamniote species, revealing conservation in vertebrate early development. Whether this conservation lends morphogenetic support to the anamniote-to-amniote transition in evolution or reflects developmental plasticity in convergent evolution awaits further investigation.
(キーワード): Animals / Cell Nucleus / Chick Embryo / Cleavage Stage, Ovum / Egg Yolk / Embryo, Nonmammalian / Embryonic Development / Gene Expression Regulation, Developmental / Giant Cells / Mitosis / Phosphorylation / Phosphoserine / RNA Polymerase II / Vertebrates / Zygote
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/dev.118604
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25742796; ● Summary page in Scopus @ Elsevier: 2-s2.0-84930703771

(DOI: 10.1242/dev.118604, PubMed: 25742796, Elsevier: Scopus)

MISC

研究者総覧に該当データはありませんでした。

総説・解説

栗栖修作, 米村重信 :
蛍光タンパク質ノックイン法の現状と細胞内局所でのタンパク質定量への応用,
細胞, Vol.55, No.5, 320-322, 2023年4月.

(キーワード): クリスパー / ノックイン / タンパク質定量 / ビンキュリン / 細胞間接着

栗栖修作, 米村重信 :
上皮細胞を支える基底膜のダイナミクス,
四国医学雑誌, Vol.77, No.1, 2, 17-24, 2021年4月.

(要約): In homeostatic epithelial tissues, the basement membrane appears to be a quiet, motionless structure. However, during embryonic development and tissue regeneration, the basement membrane dramatically changes its distribution and shows a variety of dynamics such as compositional transition and physicochemical alterations. Recently, it has been pointed out that the shape and function of epithelial tissues is greatly influenced by the way of formation and arrangement of the basement membrane. Here, we outline the current understanding of the roles of the basement membrane dynamics in epithelial morphogenesis, and briefly introduce our approach to visualize the movement of basement membrane components.
(キーワード): 基底膜 / 上皮形態形成
(徳島大学機関リポジトリ): ● Metadata: 116033
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1050006895493034368

(徳島大学機関リポジトリ: 116033, CiNii: 1050006895493034368) 鳥澤久美子, 米村重信 :
細胞間メカノトランスダクション,
生体の科学, Vol.67, No.2, 137-141, 2016年4月.

(キーワード): アドヘレンスジャンクション / メカノセンサー / α-カテニン / ビンキュリン / 張力
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390002209936236416

(CiNii: 1390002209936236416)

講演・発表

Shigenobu Yonemura :
Adjusting tension sensitivity of a-catenin for epithelial morphogenesis,
The 51st NIPS Symposium Frontiers in Epithelial Cell Biology, Okazaki, Aichi, Japan, Dec. 2021. Shigenobu Yonemura :
Adjusting Tension sensitivity of -catenin for epithelial morphogenesis,
The 51st NIPS International Symposium "Frontiers in Epithelial Cell Biology", Dec. 2021. Shigenobu Yonemura :
Force-sensing device in alpha-catenin,,
Mechanobiology, from molecules to tissue, Jun. 2016. Y Enomoto, Y Inoue, Shigenobu Yonemura and T Apache :
Three-dimensional vertex simulation on smooth surface maintenance of growing epithelial tissue based on intercellular mechano-feedback,
Biophysical Society 60th Annual Meeting, Los Angeles, California, USA, Feb. 2016.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bpj.2015.11.1654
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.bpj.2015.11.1654

(DOI: 10.1016/j.bpj.2015.11.1654) 柴田桂太朗, 浅野千帆莉, 石田紘基, 米村重信 :
磁気ピンセットを用いたメカノタキシスの詳細解析,
第8回日本メカノバイオロジー学会学術総会, 2024年2月. 米村重信, S Li, C Guan, K Fujimoto, 栗栖修作 :
細胞接着装置の形成，成熟とアクチンフィラメントおよび張力,
第8回日本メカノバイオロジー学会学術総会, 2024年2月. 米村重信 :
電子顕微鏡による受託解析の現状,
順天堂大学・日本電子株式会社合同形態学セミナー, 2023年11月. Shusaku Kurisu and Shigenobu Yonemura :
Regulation of epithelial apicobasal cell polarity by phospholipase C-beta,
第75回日本細胞生物学会大会, Jun. 2023. 浅野千帆莉, 柴田桂太朗, 石田紘基, 米村重信 :
機械的力を感知した細胞の運動変化と細胞集団に与える影響,
日本細胞生物学会大会, 2023年6月. 柴田桂太朗, 米村重信 :
上皮極性形成におけるアクチンリング構造の機能解析,
日本細胞生物学会大会, 2023年6月. 柴田桂太朗, 石田紘基, 浅野千帆莉, 米村重信 :
上皮シート張力の創傷閉鎖における機能に関するレオロジー測定,
日本メカノバイオロジー学会第7回学術総会 (北海道大学), 2023年3月. 栗栖修作, 天宅あや, 米村重信 :
大腸上皮細胞のin vitro基底膜形成における近接線維芽細胞由来IV型コラーゲンの寄与,
ムーンショット目標2 第1回若手ワークショップ, 2022年11月. 柴田桂太朗, 米村重信 :
アクチンフィラメントの流れと上皮細胞頂底極性形成との関係,
第74回日本細胞生物学会大会, 2022年6月. 栗栖修作, 天宅あや, 米村重信 :
大腸上皮細胞のin vitro基底膜形成における近接線維芽細胞由来IV型コラーゲンの寄与,
第74回日本細胞生物学会大会, 2022年6月.

(キーワード): 細胞外マトリックス (extracellular matrix) / コラーゲン (collagen) / 基底膜 / 線維芽細胞

天宅あや, 栗栖修作, 髙橋章, 米村重信 :
上皮基底膜 IV型コラーゲンの動態解析,
第94回日本生化学会大会, 2021年11月.

(キーワード): 細胞外マトリックス (extracellular matrix) / コラーゲン (collagen) / ライブイメージング

柴田桂太朗, 佐川美咲, 小嶋寛明, 米村重信, 古田健也 :
キネシンの1分子運動速度を上昇させる条件の解明,
第73回日本細胞生物学会大会, 2021年7月.

(キーワード): 生物学 (biology) / 生物物理学 / 細胞生物学 (cell biology)

栗栖修作, 米村重信 :
上皮細胞間接着のメカノセンシングにおけるアクチン結合タンパク質の量的変化,
第73回日本細胞生物学会大会, 2021年7月.

(キーワード): クリスパー・キャス9 / 上皮細胞間接着 / アクチン結合タンパク質

Shusaku Kurisu and Shigenobu Yonemura :
The roles of cortical actin rings in the establishment of epithelial cell polarity,
The 126th Annual Meeting of The Japanese Association of Anatomists, The 98th Annual Meeting of The Physiological Society of Japan, Mar. 2021.

(キーワード): アクチンリング / 上皮細胞極性

米村重信, ⻄村亮祐，加藤輝，斎⽥美佐⼦，⻲井保博，⽵⽥真宏，三好洋美，⼭形豊米村重信 :
αカテニンの張⼒に応じたビンキュリン結合制御の三次元形態形成における意義,
第5回日本メカノバイオロジー学会大会, 2021年3月. 天宅あや, 栗栖修作, 髙橋章, 米村重信 :
間質細胞由来IV型コラーゲンががん細胞に与える影響,
第262回徳島医学会学術集会, 2021年3月.

(キーワード): 基底膜 / IV型コラーゲン

米村重信 :
細胞の死に関する上皮細胞の複数反応,
第262回徳島医学会学術集会, 2021年3月. 栗栖修作, 米村重信 :
上皮細胞間接着におけるアクチン結合タンパク質の存在比とその分布,
第72回日本細胞生物学会大会, 2020年6月.

(キーワード): クリスパー・キャス9 / 上皮細胞間接着 / アクチン結合タンパク質

本田尚三, 名黒功, 米村重信 :
Analyses of SH3BP4, a novel candidate gene, found by genome-wide RNAi screening for apicobasal polarityrelated factors,
第72回日本細胞生物学会大会, 2020年6月. 米村重信, 栗栖修作，米村重信 :
Protein quanti cation at epithelial cell-cell junctions reveals a differential distribution of the actin-associated components,
第72回日本細胞生物学会大会, 2020年6月. 米村重信, 米村重信，西村亮祐 :
細胞-細胞/細胞-基質間におけるメカノセンシング,
実験医学増刊, Vol.38, No.7, 1232,-1237, 2020年5月. 本田尚三, 名黒功, 米村重信 :
上皮極性因子のゲノムワイドRNAiスクリーニングから見出された新規候補遺伝子の解析,
第19回日本蛋白質科学会年会第71回日本細胞生物学会大会合同年次大会, 2019年6月. 西村亮祐, 竹田真宏, 三好洋美, 山形豊, 米村重信 :
αカテニンの張力感受性が上皮形態形成にもたらす意義,
第19回日本蛋白質科学会年会第71回日本細胞生物学会大会合同年次大会, 2019年6月. 栗栖修作, 米村重信 :
上皮アピコベーサル境界の形成におけるアクトミオシンリングの役割,
第19回日本蛋白質科学会年会第71回日本細胞生物学会大会合同年次大会, 2019年6月.

(キーワード): 上皮極性 / アクチン細胞骨格 / イノシトールリン脂質

本田尚三, 名黒功, 米村重信 :
上皮極性因子のゲノムワイドRNAiスクリーニングによって見出された新規候補遺伝子の解析,
第4回メカノバイオロジー学会学術大会, Vol.4, No.2, 3, 2019年3月. 栗栖修作, 米村重信 :
蛍光タンパク質ノックインによる細胞間接着タンパク質の定量,
第4回日本メカノバイオロジー学会学術総会, 2019年3月.

(キーワード): 細胞間接着 / CRISPR/Cas9 / ノックイン

Shozo Honda, Isao Naguro and Shigenobu Yonemura :
Development of the RNAi screening system for apicobasal polarity factors,
Joint Annual Meeting of JSDB and JSCB, Vol.70, No.3, 12, Jun. 2018.

(要約): Epithelial cells have apicobasal polarity, which shows the asymmetric distributions of proteins between apical and basolateral surface within single cell that produce asymmetric cellular function to maintain homeostasis in the body. Therefore, apicobasal polarity is essential for multicellular organisms and its disturbance causes various diseases including cancer. Some apicobasal polarity factors have been identified in model animals through genetic studies. However, the comprehensive molecular system remains to be clarified. RNAi screening for apicobasal polarity using culturable epithelial cells has not been performed because of the robustness of epithelial sheets that protects cells from disturbance of the polarity factors. Here, we develop a screening system for apicobasal polarity factors using α-catenin-deficient R2/7 cells that are not capable of forming cell-cell adhesion. Intriguingly, R2/7 cells form the apicobasal polarity: aPKC, SCRIB and ZO-1 were localized to apical, basolateral and the boundary region, respectively. In particular, ZO-1 was observed as ring just below plasma membrane. Knockdown of known apical factors shrank the ZO-1 ring, whereas knockdown of known basolateral factors enlarged the ring. Therefore, the ZO-1 ring in R2/7 would be a good marker for sensitive detection of the change in apicobasal polarity. We established an algorithm for the detection and estimation of ZO-1 area that was ensured as acceptable assay (Z´-factor>0.5). Then we performed the screening using siRNA library (18,152 genes) and high-throughput image analysis. Using bioinformatic analyses, we could extract 1,263 and 422 candidate genes showing shrinking and enlarging type, respectively. Now, we are executing biochemical analyses for novel molecules to clarify comprehensive molecular system of the apicobasal polarity.

Shusaku Kurisu and Shigenobu Yonemura :
Determination of protein composition at epithelial cell-cell junctions by CRISPR/Cas9-mediated fluorescent protein knockin,
Joint Annual Meeting of 70th JSCB and 51st JSDB co-sponsored by APDBN, Jun. 2018.

(キーワード): CRISPR/Cas9 / 細胞間接着 / ノックイン / 上皮

米村重信 :
上皮細胞が丸くなれる仕組み,
日本顕微鏡学会北海道支部学術講演会, 2016年12月. 米村重信, 本田尚三 :
お互い接着しない上皮細胞を使って極性形成機構を探求する,
第68回日本細胞生物学会大会, 2016年6月. 榎本祥英, 井上康弘, 米村重信, 安達泰治 :
組織形状平滑化を実現する頂端収縮力調整機能の数理モデリング,
日本機械学会2015年度年次大会, 2015年9月. 米村重信 :
上皮形態形成におけるECMに対する感受性の細胞種による違い,
第67回日本細胞生物学会大会, 2015年7月.

研究会・報告書: 植野美彦, 関陽介, 矢部拓也, 米村重信, 阪上浩, 生島仁史, 藤猪英樹, 白山靖彦, 山田健一, 木下和彦, 櫻谷英治, 古屋 S. 玲, 上岡麻衣子 :
令和2年度徳島大学高等教育研究センターアドミッション部門報告書,
令和2年度徳島大学高等教育研究センターアドミッション部門報告書, 2021年3月.

特許: 研究者総覧に該当データはありませんでした。
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: 上皮シートの形成修復における細胞間接着装置の成熟とシグナリング (研究課題/領域番号: 24K02228 )
タイトジャンクションを介した上皮シートの形成と修復の分子機構 (研究課題/領域番号: 21H02684 )
上皮バリア機能を担うタイトジャンクションにおける隣接する細胞の死の感知 (研究課題/領域番号: 18H02617 )
上皮細胞の極性形成機構 (研究課題/領域番号: 15KT0086 )
三次元培養における形態を限定する加工培養基質の開発 (研究課題/領域番号: 26650071 )
上皮シート維持の分子機構 (研究課題/領域番号: 23111534 )
細胞間接着に依存しない始原的な上皮極性形成の機構 (研究課題/領域番号: 22570195 )
上皮細胞におけるカドヘリン・カテニン複合体局在化因子の探索 (研究課題/領域番号: 22570188 )
細胞間接着構造形成における、アクチン繊維の張力に依存した構成要素集積のメカニズム (研究課題/領域番号: 19036035 )
単一細胞殺傷法を用いた損傷修復並びに極性形成開始機構の研究 (研究課題/領域番号: 18657065 )
細胞間接着構造形成における構成要素集積のメカニズム (研究課題/領域番号: 17048034 )
Rhoファミリータンパク質の正確な細胞内局在の決定とがん化に伴う変化の解析 (研究課題/領域番号: 15024267 )
低分子量Gタンパク質Rhoの挙動の時間的空間的解析 (研究課題/領域番号: 13670115 )
細胞間接着の分子機構とその異常:細胞がん化・転移浸潤における役割 (研究課題/領域番号: 12219210 )
タイトジャンクションの接着分子クローディンとオクルディン:コネモシンとの比較 (研究課題/領域番号: 11694270 )
細胞の形態形成におけるERM蛋白質のリン酸化とERM結合性膜蛋白質の役割 (研究課題/領域番号: 11670117 )
細胞接着の異常と発がん・転移機構 (研究課題/領域番号: 06283225 )
膜蛋白質と細胞骨格とのERM蛋白質を介した相互作用の解析 (研究課題/領域番号: 09770072 )
細胞骨格と膜蛋白質とのERM蛋白質を介した相互作用の解析 (研究課題/領域番号: 08770085 )
細胞極性と細胞間透過性を決定する接着分子オクルディンの構造と機能 (研究課題/領域番号: 08407006 )
細胞質分裂におけるアクチン繊維と膜蛋白質(CD43とCD44)との相互作用の解析 (研究課題/領域番号: 07780637 )
微絨毛におけるアクチン繊維と膜蛋白質との相互作用の解析 (研究課題/領域番号: 06780594 )
脳血管関門の人為的制御法の開発 (研究課題/領域番号: 06557014 )
細胞間接着のよる細胞増殖と分化の制御機構 (研究課題/領域番号: 06404083 )
分裂溝におけるアクチン繊維と膜タンパク質との相互作用の解析 (研究課題/領域番号: 05780539 )
隣接する細胞間の接着特性を直接測定する装置の開発 (研究課題/領域番号: 05558091 )
細胞間接着と発がん・転移機構 (研究課題/領域番号: 05152130 )
Caged化合物を用いた時分割電子顕微鏡法のための急速凍結装置の開発 (研究課題/領域番号: 04558034 )
細胞間接着蛋白質と細胞の増殖・転移機構 (研究課題/領域番号: 04152125 )
細胞間接着装置の構造と機能に関する分子解剖学的研究 (研究課題/領域番号: 03404015 )
細胞間接着制御蛋白質と細胞の増殖・転移機構 (研究課題/領域番号: 03152130 )
研究者番号（60192811）による検索

その他: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年5月8日更新

専門分野・研究分野: 細胞生物学
所属学会・所属協会: 日本細胞生物学会
日本生物物理学会
日本分子生物学会
日本生化学会
Asian Pacific Organization of Cell Biology
委員歴・役員歴: 日本細胞生物学会 (理事,副会長 [2016年7月〜2020年6月], 代議員,編集委員 [2015年7月〜2021年6月])
日本細胞生物学会 (代議員, 編集委員)
日本生化学会 (編集委員 [2017年12月〜2019年12月])
日本細胞生物学会 (会長理事 [2020年6月〜2022年6月], 代議員編集委員)
Asian Pacific Organization of Cell Biology (財務担当 [2022年11月])
受賞: 1989年, 井上研究奨励賞 (井上科学振興財団)
活動: グループ担任 (2015年4月〜2022年3月)
医科学教育部教育・研究委員会副委員長 (2016年4月〜2018年3月)
医学部学生委員会委員 (2016年4月〜2020年3月)
総合研究支援センター先端医研部門長 (2018年4月)
医科学教育部教育・研究委員会委員長 (2018年4月〜2020年3月)
医学科入試委員会副委員長 (2019年4月〜2020年3月)
総合研究支援センターセンター長 (2019年4月〜2020年3月)
総合研究支援センターセンター長 (2020年4月〜2021年3月)
研究支援センターセンター長 (2021年4月〜2022年3月)

リサーチマップで最新データを確認するＪグローバルで最新データを確認する

2022年8月14日更新

2024年5月4日更新

Ｊグローバル

Jグローバル最終確認日: 2024/5/4 01:32
氏名（漢字）: 米村重信
氏名（フリガナ）: ヨネムラシゲノブ
氏名（英字）: Yonemura Shigenobu
所属機関: 徳島大学教授
国立研究開発法人チームリーダー

リサーチマップ

researchmap最終確認日: 2022/8/14 01:54
氏名（漢字）: 米村重信
氏名（フリガナ）: ヨネムラシゲノブ
氏名（英字）: Yonemura Shigenobu
プロフィール: リサーチマップAPIで取得できませんでした。
登録日時: 2004/11/29 00:00
更新日時: 2022/6/28 10:44
アバター画像URI: https://researchmap.jp/read0118149/avatar.jpg
ハンドル: リサーチマップAPIで取得できませんでした。
eメール: リサーチマップAPIで取得できませんでした。
eメール（その他）: リサーチマップAPIで取得できませんでした。
携帯メール: リサーチマップAPIで取得できませんでした。
性別: リサーチマップAPIで取得できませんでした。
没年月日: リサーチマップAPIで取得できませんでした。
所属ID: 0344000000
所属: 徳島大学
部署: 大学院医歯薬学研究部（医学系）
職名: 教授
学位: 理博
学位授与機関: リサーチマップAPIで取得できませんでした。
URL: リサーチマップAPIで取得できませんでした。
科研費研究者番号: リサーチマップAPIで取得できませんでした。
Google Analytics ID: リサーチマップAPIで取得できませんでした。
ORCID ID: リサーチマップAPIで取得できませんでした。
その他の所属ID: リサーチマップAPIで取得できませんでした。
その他の所属名: リサーチマップAPIで取得できませんでした。
その他の所属部署: リサーチマップAPIで取得できませんでした。
その他の所属職名: リサーチマップAPIで取得できませんでした。
最近のエントリー: リサーチマップAPIで取得できませんでした。
Read会員ID: リサーチマップAPIで取得できませんでした。
経歴: リサーチマップAPIで取得できませんでした。
受賞
Misc
論文
講演・口頭発表等: リサーチマップAPIで取得できませんでした。
書籍等出版物: リサーチマップAPIで取得できませんでした。
研究キーワード: リサーチマップAPIで取得できませんでした。
研究分野: リサーチマップAPIで取得できませんでした。
所属学協会
担当経験のある科目: リサーチマップAPIで取得できませんでした。
その他: リサーチマップAPIで取得できませんでした。
Works: リサーチマップAPIで取得できませんでした。
特許: リサーチマップAPIで取得できませんでした。
学歴: リサーチマップAPIで取得できませんでした。
委員歴: リサーチマップAPIで取得できませんでした。
社会貢献活動: リサーチマップAPIで取得できませんでした。

ＫＡＫＥＮで最新データを確認する

2024年5月4日更新

研究者番号: 60192811

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(医学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2018/4/1 – 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(医学域), 教授
2016/4/1 – 2017/4/1 : 徳島大学, 大学院医歯薬学研究部(医学系), 教授
2015/4/1 : 徳島大学, 大学院医歯薬学研究部, 教授
2015/4/1 : 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー
2014/4/1 : 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー
2010/4/1 – 2012/4/1 : 独立行政法人理化学研究所, 電子顕微鏡解析室, 室長
2007/4/1 – 2008/4/1 : 独立行政法人理化学研究所, 電子顕微鏡解析室, 室長
2007/4/1 : 理化学研究所, 電子顕微鏡解析室, 室長
2005/4/1 – 2006/4/1 : 独立行政法人理化学研究所, 細胞形態形成研究チーム, チームリーダー
2003/4/1 : 独立行政法人理化学研究所, 細胞形態形成研究チーム, チームリーダー
2002/4/1 : 理化学研究所, 細胞形態形成研究チーム, チームリーダー
2001/4/1 : 理化学研究所, 細胞形態形成研究チーム, チームリーダー(研究職)
1995/4/1 – 2000/4/1 : 京都大学, 医学研究科, 講師
1999/4/1 : 京都大学, 大学院・医学研究科, 講師
1997/4/1 : 京都大学, 大学院・医学研究科, 講師
1991/4/1 – 1994/4/1 : 岡崎国立共同研究機構, 生理学研究所, 助手

審査区分/研究分野

研究代表者

複合領域 / 基礎生物科学 / 細胞生物学
医学 / 生理 / 医化学一般
生物系 / 生物学 / 生物科学 / 細胞生物学
構成的システム生物学
生物系
小区分48040:医化学関連

研究代表者以外

生物系 / 生物学 / 生物科学 / 細胞生物学
医学 / 生理 / 解剖学一般
複合領域 / 生物物理学 / 分子遺伝学・分子生理学
複合領域 / 基礎生物科学 / 細胞生物学
医学 / 生理 / 病態医化学
生物系

キーワード

研究代表者

細胞質分裂 / アクチン繊維 / CD43 / 微絨毛 / CV1 / アクチン / 細胞膜 / CD44 / ERM / 分裂溝 / ICAM-2 / ERM蛋白質 / リン酸化 / 形態形成 / Rho / Rac / Cdc42 / がん化 / 局在 / 低分子量Gタンパク / アドヘレンスジャンクション / αカテニン / ビンキュリン / 張力 / ミオシン / 分子変形 / 損傷修復 / レーザー / 細胞接着 / 収縮 / GFP / ラメリポディア / 細胞間接着装置 / 張力依存性 / アドへレンスジャンクション / 上皮細胞 / 極性 / 細胞外基質 / 上皮極性 / 微小管 / 細胞周期 / 細胞極性 / 細胞接着装置 / 上皮シート / ATP / ギャプジャンクション / 死細胞 / アクトミオシンリング / タイトジャンクション / 微細加工 / 三次元培養 / PDMS / 細胞集合 / マイクロファブリケーション / カドヘリン / マイクロピペット / 接着分子 / 接着力 / カテニン / 細胞間接着力 / cell adhesion / cadherin / adhesion molecule / catenin / micropipet / physiology / ERM結合性膜蛋白質 / TCA固定 / PIP2 / ネオマイシン / C3 / 脱リン酸化 / トリクロロ酢酸 / ERM proteins / ERM-binding membrane proteins / microvilli / phosphorylation / TCA fixation / neomycin / TCA / LPA / EGF / 可視化 / 低分子量Gタンパク質 / 抗体 / Microvilli / cleavage furrow / 細胞間接着 / 定量生物学 / 網羅的スクリーニング / RNAi / ゲノムワイドスクリーニング / 数理解析 / 画像解析 / siRNAスクリーニング / 上皮 / 細胞死 / 上皮細胞シート / ミオシン集積 / 上皮修復 / バリア機能 / ZO-1

研究代表者以外

細胞接着 / 接着装置 / カドヘリン / アクチン / チロシンキナ-ゼ / ラディキシン / アンキリン / カテニン / がん / 転移 / アドヘレンスジャンクション / カラニン / 肝臓 / マドヘレンスジャンクション / チロシンリン酸化 / オクルディン / クローディン / ノックアウトマウス / タイトジャンクション / ERM蛋白質 / ZO-1 / エズリン / モエシン / ノックアウト / αカテニン / Rho / Rhoキナーゼ / ERM / 発がん / βカテニン / ZO-2 / 細胞間接着 / 情報伝達機構 / 癌抑制遺伝子 / ES細胞 / ラディチシン / 細胞間相互作用 / 細胞外マトリックス / 上皮極性 / F9細胞 / アドレヘンスジャンクション / ラディヲシン / 裏打ち構造 / チロシン燐酸化 / チロシンキナーゼ / モノクローナル抗体 / アドヘレンスジャンクション / 裏打ち蛋白質 / チロシリン酸化 / モノクローナル〓〓 / cell adhesion / adherens junctions / radixin / undercoat / adhesion apparatus / tyrosin phosporylation / tyrosin kinase / monoclonal antibody / Caged化合物 / 急速凍結 / 液体ヘリウム / 筋肉 / 血小板 / IP3 / 電子顕微鏡 / 時間分解能 / caged化合物 / ケージドATP / 急速凍結法 / ミオシン / 紫外線 / ミリ秒 / muscle / caged compounds / rapid freezing / liquid helium / platelet / electron microscopy / temporal resolution / Z0-1 / 相同組換え / 上皮細胞 / cadherin / ezrin / moesin / catenin / occuldin / claudin / 脳血管関門 / リン酸化 / 内皮細胞 / アンチセンスDNA / 機能阻害抗体 / 脳血管バリアー / blood-brain barrier / tight junction / occludin / knock-out / phosphrylation / endothelial cell / アドへレンスジャンクション / ドラッグデリバリー / 極性 / ターゲッティング / 細胞極性 / 自己抗体 / 接着分子 / intercellular junction / knockout / epithelial cells / コネキシン / ギャンプジャンクション / キメラ分子 / 二次元結晶 / 遺伝子発現 / ギャップジャンクション / 膜蛋白質 / 結晶化 / OCCLUDIN / CLAUDIN / CONNEXIN / TIGHT JUNCTION / GAP JUNCTION / CHIMERIC MOLECULE / CRYSTALIZATION / GENE FAMILY / 上皮間バリアー / 細胞増殖 / Snail / 上皮間葉転換 / 転移浸潤 / GFP / 血液脳関門 / メルリン / MUPP1 / PDZドメイン / 大腸癌 / α-カテニン / β-カテニン / cell-cell adhesion / ERM proteins / epidermal barrier / knockout mouse / cell proliferation

研究課題研究成果共同研究者

「研究課題をさがす」で表示
テキスト（CSV）で出力

テキスト（CSV）で出力

注目研究はありません。

研究者を探す

米村 重信

Ｊグローバル

リサーチマップ

研究代表者

研究代表者以外

研究代表者

研究代表者以外

米村重信