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

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Byron, Askari, Humphries, Jacquemet, Koper, Warwood, Choi, Stroud, Chen, Knight, Humphries
Publication year: 2015
Journal: Nature Communications
Journal acronym: Nat Commun
Volume number: 6
ISSN: 2041-1723


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.

Last updated on 2020-22-01 at 05:03