Flat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling of specific receptors
Flat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling of specific receptors
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DOI：
10.1038/ncomms16068
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发表时间：
2017-07-13
影响因子：
16.6
通讯作者：
Innocenti, Metello
中科院分区：
文献类型：
--
作者：
Leyton-Puig, Daniela;Isogai, Tadamoto;Innocenti, Metello
质膜处的网格蛋白晶格覆盖内陷区域和平坦区域，分别形成网格蛋白包被的凹坑和网格蛋白斑块。网格蛋白包被的凹坑在胞吞作用中的功能和调节已被充分了解，但网格蛋白斑块仍然是神秘的纳米结构域。在这里，我们使用超分辨率显微镜、分子遗传学和细胞生物学来证明网格蛋白斑块包含网格蛋白介导的内吞作用和细胞粘附的机制，并与网格蛋白包被的凹坑和丝状肌动蛋白相关。我们还发现，N-WASP 通过 Arp2/3 复合体促进的肌动蛋白聚合对于斑块的调节至关重要，但对于凹坑的调节则不然。网格蛋白斑块会阻碍细胞迁移，并在 LPA 受体 1（而非 EGF 受体）激活时经历肌动蛋白和 N-WASP 依赖性分解。最重要的是，斑块分解与 LPA 受体 1 的内吞作用和 AKT 活性的下调相关。因此，网格蛋白斑块充当动态肌动蛋白控制的枢纽，用于网格蛋白介导的内吞作用和表现出受体特异性的信号传导。
Clathrin lattices at the plasma membrane coat both invaginated and flat regions forming clathrin-coated pits and clathrin plaques, respectively. The function and regulation of clathrin-coated pits in endocytosis are well understood but clathrin plaques remain enigmatic nanodomains. Here we use super-resolution microscopy, molecular genetics and cell biology to show that clathrin plaques contain the machinery for clathrin-mediated endocytosis and cell adhesion, and associate with both clathrin-coated pits and filamentous actin. We also find that actin polymerization promoted by N-WASP through the Arp2/3 complex is crucial for the regulation of plaques but not pits. Clathrin plaques oppose cell migration and undergo actin- and N-WASP-dependent disassembly upon activation of LPA receptor 1, but not EGF receptor. Most importantly, plaque disassembly correlates with the endocytosis of LPA receptor 1 and down-modulation of AKT activity. Thus, clathrin plaques serve as dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling that exhibit receptor specificity.