Guo Yusong, Zanetti Giulia, Schekman Randy
Department of Molecular and Cell Biology , Howard Hughes Medical Institute, University of California-Berkeley , Berkeley , United States.
Elife. 2013 Jan 8;2:e00160. doi: 10.7554/eLife.00160.
Planar cell polarity (PCP) requires the asymmetric sorting of distinct signaling receptors to distal and proximal surfaces of polarized epithelial cells. We have examined the transport of one PCP signaling protein, Vangl2, from the trans Golgi network (TGN) in mammalian cells. Using siRNA knockdown experiments, we find that the GTP-binding protein, Arfrp1, and the clathrin adaptor complex 1 (AP-1) are required for Vangl2 transport from the TGN. In contrast, TGN export of Frizzled 6, which localizes to the opposing epithelial surface from Vangl2, does not depend on Arfrp1 or AP-1. Mutagenesis studies identified a YYXXF sorting signal in the C-terminal cytosolic domain of Vangl2 that is required for Vangl2 traffic and interaction with the μ subunit of AP-1. We propose that Arfrp1 exposes a binding site on AP-1 that recognizes the Vangl2 sorting motif for capture into a transport vesicle destined for the proximal surface of a polarized epithelial cell.DOI:http://dx.doi.org/10.7554/eLife.00160.001.
平面细胞极性（PCP）需要将不同的信号受体不对称地分选到极化上皮细胞的远端和近端表面。我们研究了一种PCP信号蛋白Vangl2在哺乳动物细胞中从反式高尔基体网络（TGN）的转运。通过RNA干扰敲低实验，我们发现GTP结合蛋白Arfrp1和网格蛋白衔接复合物1（AP-1）是Vangl2从TGN转运所必需的。相比之下，与Vangl2定位于相对上皮表面的卷曲蛋白6（Frizzled 6）从TGN的输出并不依赖于Arfrp1或AP-1。诱变研究在Vangl2的C端胞质结构域中鉴定出一个YYXXF分选信号，该信号是Vangl2运输以及与AP-1的μ亚基相互作用所必需的。我们提出，Arfrp1在AP-1上暴露一个结合位点，该位点识别Vangl2分选基序，以便将其捕获到运往极化上皮细胞近端表面的运输小泡中。DOI:http://dx.doi.org/10.7554/eLife.00160.001
