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

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Article number8672
Number of pages12
JournalNature Communications
Volume6
Issue number8672
DOIs
Accepted/In press18 Sep 2015
Published28 Oct 2015

Documents

  • Yu Cell Reports 2013

    Yu_Cell_Reorts_2013.pdf, 4.14 MB, application/pdf

    Uploaded date:03 May 2016

    Version:Final published version

    Licence:CC BY

King's Authors

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.

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