The Protein Tyrosine Phosphatase PTP1B Is Required for Efficient Delivery of N-Cadherin to the Cell Surface
The Protein Tyrosine Phosphatase PTP1B Is Required for Efficient Delivery of N-Cadherin to the Cell Surface
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DOI：
10.1091/mbc.e09-10-0880
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发表时间：
2010-04-15
影响因子：
3.3
通讯作者：
Arregui, Carlos O.
中科院分区：
文献类型：
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作者：
Hernandez, Mariana V.;Wehrendt, Diana P.;Arregui, Carlos O.
PTP 1B与成熟的N-钙粘蛋白结合，促进β-连环蛋白与复合物的结合，复合物在细胞表面的稳定表达，以及钙粘蛋白介导的粘附。在这里，我们表明，PTP 1B也需要N-钙粘蛋白前体贩运通过早期阶段的分泌途径。该功能不需要PTP 1B与前体的缔合。在PTP 1B空细胞，N-钙粘蛋白前体表现出更高的敏感性内切糖苷酶H比在细胞重建的野生型酶。它还显示了ER到高尔基体的转运和加工的较慢动力学。然而，病毒性口炎水泡糖蛋白VSV-G的运输显示PTP 1B空细胞和重组细胞之间没有差异。N-钙粘蛋白前体复合物含有类似水平的α-和β-连环蛋白，无论PTP 1B的表达。相反，相关的p120连环蛋白（p120）在PTP 1B表达的情况下显着减少。一个N-钙粘蛋白前体结构缺陷的p120结合，并在PTP 1B重建细胞中表达，表现出更高的敏感性内切糖苷酶H和较慢的动力学处理比野生型前体。我们的研究结果表明，PTP 1B促进协会的p120的N-钙粘蛋白前体，促进贩运的复杂的ER到高尔基复合体。
PTP1B bound to mature N-cadherin promotes the association of beta-catenin into the complex, the stable expression of the complex at cell surface, and cadherin-mediated adhesion. Here we show that PTP1B is also required for N-cadherin precursor trafficking through early stages of the secretory pathway. This function does not require association of PTP1B with the precursor. In PTP1B null cells, the N-cadherin precursor showed higher sensitivity to endoglycosidase H than in cells reconstituted with the wild-type enzyme. It also showed slower kinetics of ER-to-Golgi translocation and processing. Trafficking of the viral stomatitis vesicular glycoprotein, VSV-G, however, revealed no differences between PTP1B null and reconstituted cells. N-cadherin precursor complexes contained similar levels of alpha- and beta-catenin regardless of PTP1B expression. In contrast, the associated p120 catenin (p120) was significantly reduced in absence of PTP1B expression. An N-cadherin precursor construct defective in p120 binding, and expressed in PTP1B reconstituted cells, showed higher sensitivity to endoglycosidase H and slower kinetics of processing than the wild-type precursor. Our results suggest that PTP1B promotes the association of p120 to the N-cadherin precursor, facilitating the trafficking of the complex from the ER to the Golgi complex.