A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting.

Byron, Askari, Humphries, Guillaume Jacquemet, Koper, Warwood, Choi, Stroud, Chen, Knight, Humphries

Research output: Contribution to journalArticleScientificpeer-review

41 Citations (Scopus)

Abstract

Integrin activation, which is regulated by allosteric changes in receptor conformation, enables cellular responses to the chemical, mechanical and topological features of the extracellular microenvironment. A global view of how activation state converts the molecular composition of the region proximal to integrins into functional readouts is, however, lacking. Here, using conformation-specific monoclonal antibodies, we report the isolation of integrin activation state-dependent complexes and their characterization by mass spectrometry. Quantitative comparisons, integrating network, clustering, pathway and image analyses, define multiple functional protein modules enriched in a conformation-specific manner. Notably, active integrin complexes are specifically enriched for proteins associated with microtubule-based functions. Visualization of microtubules on micropatterned surfaces and live cell imaging demonstrate that active integrins establish an environment that stabilizes microtubules at the cell periphery. These data provide a resource for the interrogation of the global molecular connections that link integrin activation to adhesion signalling.
Original languageUndefined/Unknown
Pages (from-to)
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

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