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

被引:380
作者
Horton, Edward R. [1 ]
Byron, Adam [1 ,2 ]
Askari, Janet A. [1 ]
Ng, Daniel H. J. [1 ]
Millon-Fremillon, Angelique [1 ]
Robertson, Joseph [1 ]
Koper, Ewa J. [1 ]
Paul, Nikki R. [1 ]
Warwood, Stacey [3 ]
Knight, David [3 ]
Humphries, Jonathan D. [1 ]
Humphries, Martin J. [1 ]
机构
[1] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England
[2] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh Canc Res UK Ctr, Edinburgh EH4 2XR, Midlothian, Scotland
[3] Univ Manchester, Fac Life Sci, Biol Mass Spectrometry Core Facil, Manchester M13 9PT, Lancs, England
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
TRANSLATION INITIATION-FACTORS; ALPHA-ACTININ; MYOSIN-II; PROTEOMIC ANALYSIS; MESSENGER-RNA; NASCENT ADHESIONS; BINDING PROTEINS; MATRIX ADHESIONS; FOCAL ADHESIONS; CELL-MIGRATION;
D O I
10.1038/ncb3257
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 alpha-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.
引用
收藏
页码:1577 / 1587
页数:11
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