title: 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.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, 37232 Nashville, TN, USA.
authors.forename: Huapeng H
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Department of Cancer Biology, Vanderbilt University, 37232 Nashville, TN, USA Department of Pharmacology, Vanderbilt University, 37232 Nashville, TN, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Dohn
authors.affiliation: Department of Cancer Biology, Vanderbilt University, 37232 Nashville, TN, USA School of Medicine, Vanderbilt University, 37232 Nashville, TN, USA.
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Markham
authors.affiliation: School of Medicine, Vanderbilt University, 37232 Nashville, TN, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Coffey
authors.affiliation: Department of Cancer Biology, Vanderbilt University, 37232 Nashville, TN, USA al.reynolds@vanderbilt.edu.
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D048430:Cell Shape; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D054460:rho-Associated Kinases; D024507:Nonmuscle Myosin Type IIA; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin
keywords: Cadherin; Catenin; Contractility