A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Tekijät: Byron A, Askari JA, Humphries JD, Jacquemet G, Koper EJ, Warwood S, Choi CK, Stroud MJ, Chen CS, Knight D, Humphries MJ
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2015
Journal: Nature Communications
Tietokannassa oleva lehden nimi: Nature Communications
Lehden akronyymi: NAT COMMUN
Artikkelin numero: ARTN 6135
Vuosikerta: 6
Sivujen määrä: 14
ISSN: 2041-1723
DOI: https://doi.org/10.1038/ncomms7135
Tiivistelmä
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.
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
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