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Title page for ETD etd-12072015-193917


Type of Document Dissertation
Author Yu, Huapeng
URN etd-12072015-193917
Title p120-catenin controls contractility along the vertical axis of epithelial lateral membranes
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Jin Chen Committee Chair
Albert B.Reynolds Committee Member
Jonathan M. Irish Committee Member
Rebecca A. Ihrie Committee Member
William P. Tansey Committee Member
Keywords
  • contractility
  • cadherin
  • catenin
Date of Defense 2015-11-23
Availability unrestricted
Abstract
In vertebrate epithelia, p120-catenin mediates E-cadherin stability and suppression of RhoA. Genetic ablation of p120 in various epithelial tissues typically causes striking alterations in tissue function and morphology. Although these effects could very well involve p120‘s activity towards Rho, ascertaining the impact of this relationship has been complicated by the fact that p120 is also required for cell-cell adhesion. Here, we have molecularly uncoupled p120’s cadherin stabilizing- and RhoA-suppressing activity. Unexpectedly, removing p120‘s Rho-suppressing activity dramatically disrupted the integrity of the apical surface, irrespective of E-cadherin stability. The physical defect was tracked to excessive actomyosin contractility along the vertical axis of lateral membranes. Thus, we suggest that p120’s distinct activities toward E-cadherin and Rho are molecularly and functionally coupled, and this in turn enables the maintenance of cell shape in the larger context of an epithelial monolayer. Importantly, local suppression of contractility by cadherin-bound p120 appears to go beyond regulating cell shape, as loss of this activity also leads to major defects in epithelial lumenogenesis.

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