Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s42003-021-01874-z

Language：English   Publishing type：Research paper (scientific journal)  

Adherens junctions (AJs) control epithelial cell behavior, such as collective movement and morphological changes, during development and in disease. However, the molecular mechanism of AJ remodeling remains incompletely understood. Here, we report that the conformational activation of α-catenin is the key event in the dynamic regulation of AJ remodeling. α-catenin activates RhoA to increase actomyosin contractility at cell-cell junctions. This leads to the stabilization of activated α-catenin, in part through the recruitment of the actin-binding proteins, vinculin and afadin. In this way, α-catenin regulates force sensing, as well as force transmission, through a Rho-mediated feedback mechanism. We further show that this is important for stable directional alignment of multiple cells during collective cell movement by both experimental observation and mathematical modeling. Taken together, our findings demonstrate that α-catenin controls the establishment of anisotropic force distribution at cell junctions to enable cooperative movement of the epithelial cell sheet.

DOI： 10.1016/j.celrep.2018.05.070

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1073/pnas.2217561120

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1083/jcb.202009037

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1083/jcb.202106160

Event date： 2023.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：奈良県コンベンションセンター   Country：Japan  

Event date： 2022.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2021.12 - 2022.6

Language：English   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2021.6 - 2021.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：オンライン   Country：Japan  

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.

Event date： 2019.12

Language：Japanese  

Venue：福岡市   Country：Japan  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：3

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：3

Type：Competition, symposium, etc. 

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：1

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：1