Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force
Copyright policy )Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force
AbstractThe turnover of integrin receptors is critical for cell migration and adhesion dynamics. Here we find that force development at integrins regulates adaptor protein recruitment and endocytosis. Using mobile RGD (Arg-Gly-Asp) ligands on supported lipid membranes (RGD membranes) and rigid RGD ligands on glass (RGD-glass), we find that matrix force-dependent integrin signals block endocytosis. Dab2, an adaptor protein of clathrin-mediated endocytosis, is not recruited to activated integrin-beta3 clusters on RGD-glass; however, it is recruited to integrin-mediated adhesions on RGD membranes. Further, when force generation is inhibited on RGD-glass, Dab2 binds to integrin-beta3 clusters. Dab2 binding to integrin-beta3 excludes other adhesion-related adaptor proteins, such as talin. The clathrin-mediated endocytic machinery combines with Dab2 to facilitate the endocytosis of RGD-integrin-beta3 clusters. From these observations, we propose that loss of traction force on ligand-bound integrin-beta3 causes recruitment of Dab2/clathrin, resulting in endocytosis of integrins.
- King's College London United Kingdom
- King's College London, University of London
- University of Hong Kong China (People's Republic of)
- Nationl University of Singapore Singapore
- Randall Division of Cell and Molecular Biophysics United Kingdom
vesicular transport adaptor protein, Cells, Dab2 protein, protein binding, ligand, chemistry, biomechanics, Article, Mice, cell motion, lipid, clathrin, Cell Movement, Traction, beta3 integrin, biochemistry, endocytosis, Animals, Humans, animal, genetics, human, mouse, glass, traction therapy, Adaptor Proteins, Signal Transducing, Integrin beta3, Adaptor Proteins, HeLa cell line, 540, Clathrin, Endocytosis, Biomechanical Phenomena, Vesicular Transport, adhesion, Adaptor Proteins, Vesicular Transport, cytology, cells, cells and cell components, protein, Apoptosis Regulatory Proteins, metabolism, HeLa Cells, Protein Binding
vesicular transport adaptor protein, Cells, Dab2 protein, protein binding, ligand, chemistry, biomechanics, Article, Mice, cell motion, lipid, clathrin, Cell Movement, Traction, beta3 integrin, biochemistry, endocytosis, Animals, Humans, animal, genetics, human, mouse, glass, traction therapy, Adaptor Proteins, Signal Transducing, Integrin beta3, Adaptor Proteins, HeLa cell line, 540, Clathrin, Endocytosis, Biomechanical Phenomena, Vesicular Transport, adhesion, Adaptor Proteins, Vesicular Transport, cytology, cells, cells and cell components, protein, Apoptosis Regulatory Proteins, metabolism, HeLa Cells, Protein Binding
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