Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force

Cheng Han Yu, Nisha Bte Mohd Rafiq, Fakun Cao, Yuhuan Zhou, Anitha Krishnasamy, Kabir Hassan Biswas, Andrea Ravasio, Zhongwen Chen, Yu Hsiu Wang, Keiko Kawauchi, Gareth E. Jones, Michael P. Sheetz

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The 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.

Original languageEnglish (US)
Article number8672
JournalNature communications
Volume6
DOIs
StatePublished - Oct 28 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Yu, C. H., Rafiq, N. B. M., Cao, F., Zhou, Y., Krishnasamy, A., Biswas, K. H., Ravasio, A., Chen, Z., Wang, Y. H., Kawauchi, K., Jones, G. E., & Sheetz, M. P. (2015). Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force. Nature communications, 6, [8672]. https://doi.org/10.1038/ncomms9672