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

Nat Cell Biol. 2015 Dec;17(12):1577-1587. doi: 10.1038/ncb3257. Epub 2015 Oct 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Integrins
  • Paxillin
  • Proteome
  • Talin
  • Tubulin Modulators
  • Zyxin
  • Actinin
  • Vinculin
  • Nocodazole