School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Commun Biol. 2020 Mar 13;3(1):117. doi: 10.1038/s42003-020-0843-2.
Integrin receptors orchestrate cell adhesion and cytoskeletal reorganization. The endocytic mechanism of integrin-β3 receptor at the podosome remains unclear. Using viscous RGD-membrane as the model system, here we show that the formation of podosome-like adhesion promotes Dab2/clathrin-mediated endocytosis of integrin-β3. Integrin-β3 and RGD ligand are endocytosed from the podosome and sorted into the endosomal compartment. Inhibitions of podosome formation and knockdowns of Dab2 and clathrin reduce RGD endocytosis. F-actin assembly at the podosome core exhibits protrusive contact towards the substrate and results in plasma membrane invaginations at the podosome ring. BIN1 specifically associates with the region of invaginated membrane and recruits DNM2. During the podosome formation, BIN1 and DNM2 synchronously enrich at the podosome ring and trigger clathrin dissociation and RGD endocytosis. Knockdowns of BIN1 and DNM2 suppress RGD endocytosis. Thus, plasma membrane invagination caused by F-actin polymerization promotes BIN1-dependent DNM2 recruitment and facilitate integrin-β3 endocytosis at the podosome.
整合素受体协调细胞黏附和细胞骨架重组。足突处整合素-β3 受体的内吞机制仍不清楚。在这里，我们使用粘性 RGD 膜作为模型系统，表明足突样黏附的形成促进了整合素-β3 的 Dab2/网格蛋白介导的内吞作用。整合素-β3 和 RGD 配体从足突中被内吞，并被分拣到内体隔室中。足突形成的抑制和 Dab2 和网格蛋白的敲低减少了 RGD 的内吞作用。足突核心处的 F-肌动蛋白组装向底物呈现突出接触，导致足突环处的质膜内陷。BIN1 特异性与内陷膜的区域结合，并募集 DNM2。在足突形成过程中，BIN1 和 DNM2 同步富集在足突环处，并触发网格蛋白解离和 RGD 内吞作用。BIN1 和 DNM2 的敲低抑制了 RGD 的内吞作用。因此，由 F-肌动蛋白聚合引起的质膜内陷促进了 BIN1 依赖性 DNM2 的募集，并促进了整合素-β3 在足突处的内吞作用。
