Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly

Edward R Horton, Adam Byron, Janet A Askari, Daniel H J Ng, Angélique Millon-Frémillon, Joseph Robertson, Ewa J Koper, Nikki R Paul, Stacey Warwood, David Knight, Jonathan D Humphries, Martin J Humphries

Research output: Contribution to journalArticlepeer-review

Abstract

Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome is likely to represent a core cell adhesion machinery, centred around four axes comprising ILK–PINCH–kindlin, FAK–paxillin, talin–vinculin and α-actinin–zyxin–VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community.
Original languageEnglish
Pages (from-to)1577-1587
JournalNature Cell Biology
Volume17
Issue number12
Early online date19 Oct 2015
DOIs
Publication statusPublished - Dec 2015

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