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

doi:10.1038/ncomms9672

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

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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 language	English
Article number	8672
Number of pages	12
Journal	Nature Communications
Volume	6
Issue number	8672
DOIs	https://doi.org/10.1038/ncomms9672
Publication status	Published - 28 Oct 2015

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Yu Cell Reports 2013Final published version, 4.14 MBLicence: CC BY

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title = "Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force",

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.",

author = "Cheng-han Yu and Rafiq, {Nisha Bte Mohd} and Fakun Cao and Yuhuan Zhou and Anitha Krishnasamy and Biswas, {Kabir Hassan} and Andrea Ravasio and Zhongwen Chen and Yu-Hsiu Wang and Keiko Kawauchi and Jones, {Gareth E.} and Sheetz, {Michael P.}",

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doi = "10.1038/ncomms9672",

language = "English",

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T1 - Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force

AU - Yu, Cheng-han

AU - Rafiq, Nisha Bte Mohd

AU - Cao, Fakun

AU - Zhou, Yuhuan

AU - Krishnasamy, Anitha

AU - Biswas, Kabir Hassan

AU - Ravasio, Andrea

AU - Chen, Zhongwen

AU - Wang, Yu-Hsiu

AU - Kawauchi, Keiko

AU - Jones, Gareth E.

AU - Sheetz, Michael P.

PY - 2015/10/28

Y1 - 2015/10/28

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms9672

DO - 10.1038/ncomms9672

M3 - Article

C2 - 26507506

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

IS - 8672

M1 - 8672

ER -

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

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