α-Catenin Controls the Anisotropy of Force Distribution at Cell-Cell Junctions during Collective Cell Migration

Cell Rep. 2018 Jun 19;23(12):3447-3456. doi: 10.1016/j.celrep.2018.05.070.

Abstract

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.

Keywords: adherens junction; collective cell migration; tension; α-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / metabolism*
  • Animals
  • Anisotropy
  • Biomechanical Phenomena
  • Cell Count
  • Cell Movement*
  • Dogs
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Formins / metabolism
  • HEK293 Cells
  • Humans
  • Madin Darby Canine Kidney Cells
  • Microfilament Proteins / metabolism
  • Models, Biological
  • Mutation
  • Protein Conformation
  • Signal Transduction
  • Vinculin / metabolism
  • alpha Catenin / chemistry
  • alpha Catenin / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Formins
  • Microfilament Proteins
  • afadin
  • alpha Catenin
  • Vinculin
  • rhoA GTP-Binding Protein