p120-Catenin Inhibits VE-Cadherin Internalization through a Rho-independent Mechanism
p120-Catenin Inhibits VE-Cadherin Internalization through a Rho-independent Mechanism
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DOI：
10.1091/mbc.e08-07-0735
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发表时间：
2009-04-01
影响因子：
3.3
通讯作者：
Kowalczyk, Andrew P.
中科院分区：
文献类型：
--
作者：
Chiasson, Christine M.;Wittich, Kristin B.;Kowalczyk, Andrew P.
p120-连环蛋白是钙粘蛋白的细胞质结合配偶体，并通过防止钙粘蛋白内吞和降解而作为钙粘蛋白表达的设定点。已知p120通过抑制RhoA活性来调节细胞运动性和侵袭性。然而，p120的这些功能之间的关系尚不清楚。在这里，我们提供的证据表明，p120功能的一部分，质膜保留机制VE-钙粘蛋白，防止招聘VE-钙粘蛋白进入膜结构域丰富的内吞机制的组成部分，包括网格蛋白和适配器复合物AP-2。p120调节VE-钙粘蛋白进入内吞区室的机制依赖于p120与钙粘蛋白跨膜结构域的相互作用，但独立于p120对Rho GT3活性的阻止而发生。这些发现阐明了p120在稳定VE-钙粘蛋白在质膜的功能机制，并证明了p120在调节钙粘蛋白进入网格蛋白依赖性内吞途径的可用性方面的新作用。
p120-catenin is a cytoplasmic binding partner of cadherins and functions as a set point for cadherin expression by preventing cadherin endocytosis, and degradation. p120 is known to regulate cell motility and invasiveness by inhibiting RhoA activity. However, the relationship between these functions of p120 is not understood. Here, we provide evidence that p120 functions as part of a plasma membrane retention mechanism for VE-cadherin by preventing the recruitment of VE-cadherin into membrane domains enriched in components of the endocytic machinery, including clathrin and the adaptor complex AP-2. The mechanism by which p120 regulates VE-cadherin entry into endocytic compartments is dependent on p120's interaction with the cadherin juxtamembrane domain, but occurs independently of p120's prevention of Rho GTPase activity. These findings clarify the mechanism for p120's function in stabilizing VE-cadherin at the plasma membrane and demonstrate a novel role for p120 in modulating the availability of cadherins for entry into a clathrin-dependent endocytic pathway.