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.

中文翻译：

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平坦的网格蛋白晶格是动态的肌动蛋白控制的枢纽，用于网格蛋白介导的内吞作用和特定受体的信号传导。

质膜上的网格蛋白晶格覆盖了内陷的和平坦的区域，分别形成了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内吞作用中的功能和调节已广为人知，但网格蛋白斑块仍是神秘的纳米域。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显示网格蛋白斑块包含网格蛋白介导的内吞作用和细胞粘附机制，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复合物促进的肌动蛋白聚合对于噬斑的调节至关重要，但对凹坑的调节至关重要。网格蛋白斑块阻止细胞迁移，并在激活LPA受体1（而不是EGF受体）后经历肌动蛋白和N-WASP依赖性拆卸。最重要的是，斑块拆卸与LPA受体1的内吞作用和AKT活性的下调有关。因此，网格蛋白斑作为网格蛋白介导的内吞作用和信号传导的动态肌动蛋白控制的枢纽，表现出受体特异性。