Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Universidad de San Martín, 1650 San Martín, Buenos Aires, Argentina.
Mol Biol Cell. 2010 Apr 15;21(8):1387-97. doi: 10.1091/mbc.e09-10-0880. Epub 2010 Feb 24.
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.
PTP1B 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黏附。在这里，我们表明 PTP1B 对于 N-钙粘蛋白前体在分泌途径的早期阶段的运输也是必需的。这个功能不需要 PTP1B 与前体的结合。在 PTP1B 缺失细胞中，N-钙粘蛋白前体比用野生型酶重建的细胞对内切糖苷酶 H 更敏感。它也表现出较慢的 ER 到高尔基体易位和加工的动力学。然而，病毒性口炎病毒囊膜糖蛋白（VSV-G）的转运在 PTP1B 缺失和重建细胞之间没有显示出差异。N-钙粘蛋白前体复合物无论 PTP1B 的表达如何，都包含相似水平的α-和β-连环蛋白。相比之下，在缺乏 PTP1B 表达的情况下，相关的 p120 连环蛋白（p120）显著减少。在 PTP1B 重建细胞中表达的、与 p120 结合缺陷的 N-钙粘蛋白前体构建体，比野生型前体对内切糖苷酶 H 更敏感，并且加工动力学更慢。我们的结果表明，PTP1B 促进 p120 与 N-钙粘蛋白前体的结合，促进复合物从 ER 向高尔基体复合物的运输。
