Role of p120-catenin in cadherin trafficking

Abstract

p120-catenin (p120) has emerged over the past several years as an important regulatory component of the cadherin adhesive complex. A core function of p120 in mammalian cells is to stabilize cadherins at the cell membrane by modulating cadherin membrane trafficking and degradation. In this way, p120 levels act as a set point mechanism that tunes cell-cell adhesive interactions. The primary control point for this regulatory activity appears to be at the level of cadherin internalization from the plasma membrane, although p120 may also impact other aspects of cadherin trafficking and turnover. In the following review, the general mechanisms of cadherin trafficking are discussed, and models for how p120 may influence cadherin membrane dynamics are presented. In one model, p120 may function as a "cap" to bind the cadherin cytoplasmic tail and prevent cadherin interactions with endocytic membrane trafficking machinery. Alternatively, p120 may stabilize cell junctions or regulate membrane trafficking machinery through interactions with small GTPases such as Rho A, Rac and Cdc42. Through these mechanisms p120 exerts influence over a wide range of biological processes that are dependent upon tight regulation of cell surface cadherin levels.

The importance of E-cadherin binding partners to evaluate the pathogenicity of E-cadherin missense mutations associated to HDGC

“…[23][24][25][26] This pathway controls the amount of E-cadherin present at the PM and p120 is considered its main regulator. 23,24,26,43,44 In order to investigate whether E-cadherin mutations could be more unstable at the PM due to the lack of p120-catenin binding and stabilization, we selected and analyzed five cytoplasmic missense mutations -R749W, E757K, E781D, P799R and V832M -and two extracellular missense mutations -T340A and A634V (Figure 1).…”

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm

“…p120 catenin and b-catenin are the prototypic members of a small family of armadillo repeat domain proteins (Daniel and Reynolds, 1995;Hatzfeld and Nachtsheim, 1996;Hatzfeld et al, 2003;Gu et al, 2009;Zhao et al, 2011). All p120 catenins and ARVCF bind the intracellular juxtamembrane region of the cytoplasmic tail of cadherins to maintain strong cell-cell adhesion (Fujimori and Takeichi, 1993;Reynolds et al, 1996;Ireton et al, 2002;Davis et al, 2003;Kausalya et al, 2004;Xiao et al, 2007;Ishiyama et al, 2010). There are four members of the p120 catenin gene family in zebrafish: ARVCF, p120 catenin d1, p120 catenin d2a (also known as NPRAP/Neurojungin), and p120 catenin d2b (also known as Delta-catenin, plakophilin 4 (PKP4), and p0071 catenin).…”

“…ARVCF and p120 catenin d1 diverged from the p120 catenin d2 proteins to bind Rho GTPases during chordate evolution (Zhao et al 2011). Besides stabilizing cadherin, p120 catenin d1 regulates cell motility by activating Cdc42 and Rac1 GTPases and inhibiting RhoA GTPase (Anastasiadis andReynolds., 2000, 2001;Anastasiadis, 2007;Grosheva et al, 2001;Magie et al, 2002;Xiao et al, 2007;McCrea and Park, 2007;Johnson et al, 2010). Consequently, p120 catenin d1 overexpression in cells results in branching filopodia and/or abnormal extension of lamellipodia through the activation of Cdc42 and Rac1 GTPases (Noren et al, 2000).…”

Making and breaking contacts: the cellular biology of cadherin regulation

“…Like other integral membrane proteins, newlysynthesized cadherins are packaged in the Golgi, transported to the cell surface and eventually internalised and degraded [1,2]. But in-between is a complex network of trafficking pathways that provide alternative routes for the endocytosis and subsequent fate of internalised cadherin (Fig 1).…”