Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs.
Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs.
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DOI：
10.1091/mbc.e12-12-0895
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发表时间：
2013-09
影响因子：
3.3
通讯作者：
Tamkun MM
中科院分区：
文献类型：
--
作者：
Fox PD;Haberkorn CJ;Weigel AV;Higgins JL;Akin EJ;Kennedy MJ;Krapf D;Tamkun MM
本研究探讨的假设，膜蛋白的运输发生在质膜（PM）域附近的底层皮质内质网（cER）。作者观察到转铁蛋白受体和水泡性口炎病毒G蛋白的胞吐作用优先发生在cER富集的PM结构域（>80%）。他们还报道了在这些区域中网格蛋白包被的凹坑的优先（>80%）定位。在哺乳动物细胞中，皮质内质网（cER）是一个与质膜（PM）紧密并列的小管和导管网络。我们提供的证据表明，PM结构域丰富的基础cER功能作为交通枢纽的插入和删除PM蛋白在HEK 293细胞。通过同时可视化cER和各种跨膜蛋白货物与全内反射荧光显微镜，我们证明了大多数的胞吐递送事件的回收膜蛋白或膜蛋白被交付到PM的第一次发生在富含cER的区域。同样，我们观察到经常性的网格蛋白簇和PM蛋白的功能性内吞作用优先在cER富集区域。因此，cER网络用于组织插入和去除细胞表面蛋白的分子机制，突出了这些独特的细胞微结构域在膜运输中的新作用。
This study investigates the hypothesis that trafficking of membrane proteins occurs at plasma membrane (PM) domains adjacent to underlying cortical endoplasmic reticulum (cER). The authors observe exocytosis of transferrin receptor and vesicular stomatitis virus G-protein to occur preferentially (>80%) at cER-enriched PM domains. They also report a preferential (>80%) localization of clathrin-coated pits at these domains. In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of tubules and cisterns that lie in close apposition to the plasma membrane (PM). We provide evidence that PM domains enriched in underlying cER function as trafficking hubs for insertion and removal of PM proteins in HEK 293 cells. By simultaneously visualizing cER and various transmembrane protein cargoes with total internal reflectance fluorescence microscopy, we demonstrate that the majority of exocytotic delivery events for a recycled membrane protein or for a membrane protein being delivered to the PM for the first time occur at regions enriched in cER. Likewise, we observed recurring clathrin clusters and functional endocytosis of PM proteins preferentially at the cER-enriched regions. Thus the cER network serves to organize the molecular machinery for both insertion and removal of cell surface proteins, highlighting a novel role for these unique cellular microdomains in membrane trafficking.