Vangl2 regulates E-cadherin in epithelial cells.

Vangl2 regulates E-cadherin in epithelial cells.
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DOI:
10.1038/srep06940
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发表时间:
2014-11-06
期刊:
影响因子:
4.6
通讯作者:
Kishi M
Kishi M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nagaoka T;Inutsuka A;Begum K;Bin hafiz Km;Kishi M

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E-钙粘蛋白属于钙依赖性细胞粘附分子的经典钙粘蛋白亚家族,对上皮粘附连接的形成和功能至关重要。在这项研究中,我们证明,Vangl 2,脊椎动物的平面细胞极性(PCP)的调节器,控制上皮细胞中的E-钙粘蛋白。E-钙粘蛋白与来自胚胎肾提取物的Vangl 2共免疫沉淀,并且在转染的成纤维细胞中也观察到这种关联。Vangl 2在过表达时增强E-钙粘蛋白的内化。相反,在来源于Vangl 2Lpt/+突变小鼠的培养的肾上皮细胞中,暴露于细胞表面的E-钙粘蛋白的定量比率增加。有趣的是,Vangl 2也通过涉及Rab 5和动力蛋白依赖性内吞作用的蛋白质运输内化。结合最近关于Frizzled 3、MMP 14和nephrin转运的报道,这些结果表明Vangl 2的分子功能之一是以广泛的选择性增强特异性质膜蛋白的内化。该功能可能参与细胞间PCP信号传导的控制或参与PCP相关的细胞粘附重排。
E-cadherin belongs to the classic cadherin subfamily of calcium-dependent cell adhesion molecules and is crucial for the formation and function of epithelial adherens junctions. In this study, we demonstrate that Vangl2, a vertebrate regulator of planar cell polarity (PCP), controls E-cadherin in epithelial cells. E-cadherin co-immunoprecipitates with Vangl2 from embryonic kidney extracts, and this association is also observed in transfected fibroblasts. Vangl2 enhances the internalization of E-cadherin when overexpressed. Conversely, the quantitative ratio of E-cadherin exposed to the cell surface is increased in cultured renal epithelial cells derived from Vangl2Lpt/+ mutant mice. Interestingly, Vangl2 is also internalized through protein traffic involving Rab5- and Dynamin-dependent endocytosis. Taken together with recent reports regarding the transport of Frizzled3, MMP14 and nephrin, these results suggest that one of the molecular functions of Vangl2 is to enhance the internalization of specific plasma membrane proteins with broad selectivity. This function may be involved in the control of intercellular PCP signalling or in the PCP-related rearrangement of cell adhesions.
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