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Cell Rep ; 23(12): 3447-3456, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29924989

RESUMO

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.


Assuntos
Junções Aderentes/metabolismo , Movimento Celular , alfa Catenina/metabolismo , Animais , Anisotropia , Fenômenos Biomecânicos , Contagem de Células , Cães , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Forminas/metabolismo , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Proteínas dos Microfilamentos/metabolismo , Modelos Biológicos , Mutação , Conformação Proteica , Transdução de Sinais , Vinculina/metabolismo , alfa Catenina/química , Proteína rhoA de Ligação ao GTP/metabolismo
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