Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells.
Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells.
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DOI：
10.1083/jcb.200306001
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发表时间：
2003-11-10
期刊：
影响因子：
--
通讯作者：
Kowalczyk AP
中科院分区：
文献类型：
--
作者：
Xiao K;Allison DF;Buckley KM;Kottke MD;Vincent PA;Faundez V;Kowalczyk AP
连环蛋白调节钙粘蛋白功能的机制尚未完全了解，p120连环蛋白（p120 ctn）的确切功能仍然特别难以捉摸。在微血管内皮细胞中，p120 ctn与细胞表面VE-钙粘蛋白广泛共定位，但未能与已进入细胞内降解区室的VE-钙粘蛋白共定位。为了测试p120 ctn与VE-钙粘蛋白结合调节VE-钙粘蛋白内化的可能性，进行了一系列方法来操纵p120 ctn对内源性VE-钙粘蛋白的可用性。竞争p120 ctn结合的VE-钙粘蛋白突变体的表达引发内源性VE-钙粘蛋白的降解。类似地，使用siRNA降低p120 ctn水平引起VE-钙粘蛋白细胞水平的显著和剂量相关的降低。与此相反，p120 ctn的过表达增加VE-钙粘蛋白细胞表面水平和抑制进入细胞表面VE-钙粘蛋白降解室。这些结果表明，细胞水平的p120 ctn功能作为一个设定点的机制，调节钙粘蛋白的表达水平，和p120 ctn的主要功能是控制钙粘蛋白的内化和降解。
The mechanisms by which catenins regulate cadherin function are not fully understood, and the precise function of p120 catenin (p120ctn) has remained particularly elusive. In microvascular endothelial cells, p120ctn colocalized extensively with cell surface VE-cadherin, but failed to colocalize with VE-cadherin that had entered intracellular degradative compartments. To test the possibility that p120ctn binding to VE-cadherin regulates VE-cadherin internalization, a series of approaches were undertaken to manipulate p120ctn availability to endogenous VE-cadherin. Expression of VE-cadherin mutants that competed for p120ctn binding triggered the degradation of endogenous VE-cadherin. Similarly, reducing levels of p120ctn using siRNA caused a dramatic and dose-related reduction in cellular levels of VE-cadherin. In contrast, overexpression of p120ctn increased VE-cadherin cell surface levels and inhibited entry of cell surface VE-cadherin into degradative compartments. These results demonstrate that cellular levels of p120ctn function as a set point mechanism that regulates cadherin expression levels, and that a major function of p120ctn is to control cadherin internalization and degradation.
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DOI：
10.1083/jcb.118.3.671
发表时间：
1992-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Knudsen KA;Wheelock MJ
通讯作者：
Wheelock MJ
影响因子：
64.5
作者：
HEASMAN, J;CRAWFORD, A;WYLIE, C
通讯作者：
WYLIE, C
影响因子：
15.9
作者：
Conacci-Sorrell, M;Zhurinsky, J;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A
影响因子：
7.8
作者：
Albelda, S M;Muller, W A;Buck, C A;Newman, P J
通讯作者：
Newman, P J
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R