Research Seminar: Proteomic definition of the integrin-actin nexus and the mechanism for adhesion remodeling in G2-phase of the cell cycle
11 October 2017
Professor Martin Humphries, Wellcome Centre for Cell-Matrix Research, University of Manchester
Tuesday 17th October, 1.00 p.m., Stacey Lecture Theatre 1
Integrin adhesion complexes (IACs) are mechanochemical signalling hubs that transduce signals to regulate proliferation, differentiation and migration. We have integrated several IAC proteomes and used this dataset to identify core and associated components from a range of functional protein classes. To investigate the robustness of this IAC network, the effects of pharmacological perturbation of FAK and Src were examined. We conclude that the IAC is a stable structural connection, which is nonetheless able to relay dynamic signals to functional end-points via phosphorylation. Before mitosis, IACs are disassembled and at mitosis cells round up. The molecular mechanism that links the cell cycle machinery to the initial loss of adhesion is unknown. We have found that CDK1 has an interphase role in promoting adhesion complex organisation. Disassembly of adhesion complexes in G2 is associated with CDK1-cyclin B1 binding and CDK1 inactivation. Thus, CDK1 inhibition is the trigger that initiates adhesion remodeling prior to mitosis.