Clathrin-mediated endocytosis occurs via the assembly of clathrin-coated pits (CCPs) that invaginate and pinch off to form clathrin-coated vesicles (CCVs). It is well known that adaptor protein 2 (AP2) complexes trigger clathrin assembly on the plasma membrane, and biochemical and structural studies have revealed the nature of these interactions. Numerous endocytic accessory proteins collaborate with clathrin and AP2 to drive CCV formation. However, many questions remain as to the molecular events involved in CCP initiation, stabilization, and curvature generation. Indeed, a plethora of recent evidence derived from cell perturbation, correlative light and EM tomography, live-cell imaging, modeling, and high-resolution structural analyses has revealed more complexity and promiscuity in the protein interactions driving CCP maturation than anticipated. After briefly reviewing the evidence supporting prevailing models, we integrate these new lines of evidence to develop a more dynamic and flexible model for how redundant, dynamic, and competing protein interactions can drive endocytic CCV formation and suggest new approaches to test emerging models.

中文翻译：

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用于组装和塑造网格蛋白涂层凹坑的不断发展的模型


网格蛋白介导的内吞作用是通过网格蛋白包被的小坑（CCP）组装而发生的，这些小坑内陷并夹断形成网格蛋白包被的囊泡（CCV）。众所周知，衔接蛋白 2 (AP2) 复合物会触发质膜上的网格蛋白组装，生化和结构研究已经揭示了这些相互作用的本质。许多内吞辅助蛋白与网格蛋白和 AP2 合作驱动 CCV 形成。然而，关于 CCP 启动、稳定和曲率生成所涉及的分子事件仍然存在许多问题。事实上，最近来自细胞扰动、相关光和电磁断层扫描、活细胞成像、建模和高分辨率结构分析的大量证据揭示了驱动 CCP 成熟的蛋白质相互作用比预期更加复杂和混杂。在简要回顾了支持流行模型的证据后，我们整合了这些新的证据，以开发一个更加动态和灵活的模型，用于说明冗余、动态和竞争性蛋白质相互作用如何驱动内吞 CCV 形成，并提出测试新兴模型的新方法。