Podosome formation promotes plasma membrane invagination and integrin-β3 endocytosis on a viscous RGD-membrane

• Published in: Communications biology 2020-03, Vol.3 (1), p.117-117, Article 117
• Main Authors: Cao, Fakun, Zhou, Yuhuan, Liu, Xiaoting, Yu, Cheng-han
• Format: Article
• Language: English
• Subjects: 14/1; 14/19; 14/35; 38/109; 38/70; 38/89; 631/57/1461; 631/80/128; 631/80/79; Actin; Actins - metabolism; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adaptor Proteins, Vesicular Transport - genetics; Adaptor Proteins, Vesicular Transport - metabolism; Animals; Biology; Biomedical and Life Sciences; Cell Adhesion; Cell adhesion & migration; Cell Membrane - metabolism; Cells, Cultured; Clathrin; Clathrin - genetics; Clathrin - metabolism; Cytoskeleton; Dynamin; Dynamin II - genetics; Dynamin II - metabolism; Endocytosis; Endocytosis - genetics; Fibroblasts - metabolism; Gene Knockdown Techniques; Humans; Integrin beta3 - genetics; Integrin beta3 - metabolism; Invaginations; Life Sciences; Ligands; Membranes, Artificial; Mice; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oligopeptides - metabolism; Podosomes - metabolism; Polymerization; Rats; Transfection; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 2399-3642; 2399-3642
• 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. Cao et al. investigate the mechanism of integrin-β3 endocytosis on podosomes from cells on viscous RGD- membranes. By using live imaging, the authors monitor actin and membrane dynamics during podosome formation and show that integrin-β3/RGD endocytosis is DAB2/clathrin mediated and dynamin-2 and BIN1 dependent.