p120-catenin controls contractility along the vertical axis of epithelial lateral membranes

Abstract

In vertebrate epithelia, p120-catenin (hereafter referred to as p120; also known as CTNND1) 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 activites. 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 towards 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.

ROCK1 but not ROCK2 contributes to RhoA signaling and NMIIA-mediated contractility at the epithelial zonula adherens

“…To substantiate this notion, we then used a location biosensor for GTP-RhoA, GFP-AHPH (Piekny and Glotzer, 2008; Priya et al. , 2015; Yu et al. , 2016).…”

Rho GTPases and actomyosin: Partners in regulating epithelial cell-cell junction structure and function

“…p120 appears to coordinate RhoA/Rac1 antagonism as it can inactivate RhoA through p190RhoGAP-B recruitment and stimulate Rac1 and Cdc42 activation though the GEF Vav2 (Noren et al, 2000; Ponik et al, 2013; Valls et al, 2012; Wildenberg et al, 2006; Zebda et al, 2013). Interestingly, downregulation of RhoA through p120 catenin requires cadherin association (Yu et al, 2016), whereas upregulation of Rac1 and Cdc42 requires unbound p120 catenin (Noren et al, 2000; Valls et al, 2012). Additionally, p120 can bind directly to RhoA-GDP in vitro and suppress GTP exchange, functioning similarly to Rho GDI (Anastasiadis et al, 2000).…”

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

“…Removing p120's Rho-suppressing activity lead to excessive actomyosin contractility along the vertical axis of cells and disrupted the integrity of the apical surface, irrespective of Ecadherin stability (Yu et al 2016). Interestingly, p120 has been described to associate with desmosomes during their formation in a Ca 2þ -shift experiment (Kanno et al 2008).…”