記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Cell Biology  

The epithelial cell sheet functions as a barrier to prevent invasion of pathogens. It is necessary to eliminate intercellular gaps not only at bicellular junctions, but also at tricellular contacts, where three cells meet, to maintain epithelial barrier function. To that end, tight junctions between adjacent cells must associate as closely as possible, particularly at tricellular contacts. Tricellulin is an integral component of tricellular tight junctions (tTJs), but the molecular mechanism of its contribution to the epithelial barrier function remains unclear. In this study, we revealed that tricellulin contributes to barrier formation by regulating actomyosin organization at tricellular junctions. Furthermore, we identified α-catenin, which is thought to function only at adherens junctions, as a novel binding partner of tricellulin. α-catenin bridges tricellulin attachment to the bicellular actin cables that are anchored end-on at tricellular junctions. Thus, tricellulin mobilizes actomyosin contractility to close the lateral gap between the TJ strands of the three proximate cells that converge on tricellular junctions.

DOI： 10.1083/jcb.202009037

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Cell Biology  

Epithelial cells are constantly exposed to osmotic stress. The influx of water molecules into the cell in a hypo-osmotic environment increases plasma membrane tension as it rapidly expands. Therefore, the plasma membrane must be supplied with membrane lipids since expansion beyond its elastic limit will cause the cell to rupture. However, the molecular mechanism to maintain a constant plasma membrane tension is not known. In this study, we found that the apical membrane selectively expands when epithelial cells are exposed to hypo-osmotic stress. This requires the activation of mTORC2, which enhances the transport of secretory vesicles containing sphingomyelin, the major lipid of the apical membrane. We further show that the mTORC2–Rab35 axis plays an essential role in the defense against hypotonic stress by promoting the degradation of the actin cortex through the up-regulation of PI(4,5)P2 metabolism, which facilitates the apical tethering of sphingomyelin-loaded vesicles to relieve plasma membrane tension.

DOI： 10.1083/jcb.202106160

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41467-020-20826-5

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1091/mbc.E15-09-0670

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1083/jcb.201412075

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1091/mbc.E14-09-1382

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1083/jcb.201202041

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1091/mbc.E11-03-0274

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1242/jcs.046649

開催年月日： 2021年12月 - 2022年6月

記述言語：英語  

開催地：オンライン   国名：日本国  

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開催年月日： 2021年6月 - 2021年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：オンライン   国名：日本国  

Multicellular tissues are covered by a continuous sheet of epithelial cells. The epithelial cells adhere to each other through cell adhesion structures, the apical junctional complexes (AJC), that are reinforced by a network of actomyosin filaments. Contractility of the actomyosin network drives the constriction of the apical plasma membrane, a hallmark of epithelial cells that underlies cell shape changes during developmental morphogenesis and maintenance of tissue integrity in homeostasis. However, it is unclear how the core components of the AJC modulate apical contractility in the broader context of the epithelial cell sheet. In this study, we present evidence that the membrane-associated guanylate kinases (MAGUK) family proteins MAGI-1 and MAGI-3 are key negative regulators of apical membrane contractility. We find that MAGI knockout in a model epithelial cell line enriches non-muscle myosin IIB (NMIIB) as well as the myosin activator Rho-associated protein kinase 1 (ROCK1) at AJC. As a result of the heightened cellular contractility, the MAGI knockout cell sheet is populated by cells having irregularly sized apical domains. Members of MAGI proteins are differentially recruited to the AJC by the scaffolding proteins afadin and the zonula occludens (ZO) family proteins. MAGI then recruit ankyrin-repeat-, SH3-domain- and proline-rich-region-containing protein 2 (ASPP2), which in turn controls the localizations of the polarity proteins Partitioning defective-3 (Par-3) and atypical protein kinase C (aPKC) at AJC. We further clarify the functional interaction between ASPP2 and Par-3 by elucidating the requirement for ASPP2 recruitment of protein phosphatase 1 (PP1) to retain aPKC at AJC, which is necessary to antagonize ROCK. These results taken together indicate that homeostasis of the epithelial sheet morphology requires conformity of two factors within a certain range by the constituent cells: junctional ROCK activity and NMIIB recruitment. Finally, signaling from AJC to Par-3-aPKC through MAGI is a crucial means of normalizing this activity level, owing to MAGIs’ role in regulating local phosphorylation dynamics through ASPP2-PP1.

開催年月日： 2019年12月

記述言語：日本語  

開催地：福岡市   国名：日本国  

開催年月日： 2019年6月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2019年6月

記述言語：英語  

国名：日本国  

記述言語：日本語