A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Jacquemet G; Humphries JD; Byron A; Choi CK; Askari JA; Stroud MJ; Koper EJ; Warwood S; Knight D; Humphries MJ; Chen CS
A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Jacquemet G
Humphries JD
Byron A
Choi CK
Askari JA
Stroud MJ
Koper EJ
Warwood S
Knight D
Humphries MJ
Chen CS
NATURE PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042716092
https://urn.fi/URN:NBN:fi-fe2021042716092
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.
Kokoelmat
- Rinnakkaistallenteet [19207]