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

Edward Horton, A. Byron, Janet Askari, D.H.J. Ng, A. Millon-Frémillon, J. Robertson, E.J. Koper, N.R. Paul, Stacey Warwood, David Knight, Jonathan 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
Number of pages11
JournalNature Cell Biology
Volume17
Issue number12
DOIs
Publication statusPublished - 19 Oct 2015

Keywords

  • Actinin
  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cells, Cultured
  • Cluster Analysis
  • Focal Adhesions
  • Humans
  • Immunoblotting
  • Integrins
  • K562 Cells
  • Kinetics
  • Mass Spectrometry
  • Mice
  • Microscopy, Fluorescence
  • Nocodazole
  • Paxillin
  • Protein Interaction Maps
  • Proteome
  • Proteomics
  • Talin
  • Tubulin Modulators
  • Vinculin
  • Zyxin

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