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Proteomic analysis of α4β1 integrin adhesion complexes reveals α‐subunit‐dependent protein recruitment
Author(s) -
Byron Adam,
Humphries Jonathan D.,
Craig Sue E.,
Knight David,
Humphries Martin J.
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201100487
Subject(s) - integrin , microbiology and biotechnology , biology , cell adhesion , cytoplasm , cd49c , integrin, beta 6 , cell adhesion molecule , signal transduction , extracellular matrix , proteome , focal adhesion , colocalization , integrin alpha m , collagen receptor , adhesion , protein subunit , receptor , cell , chemistry , biochemistry , gene , organic chemistry
Integrin adhesion receptors mediate cell–cell and cell–extracellular matrix interactions, which control cell morphology and migration, differentiation, and tissue integrity. Integrins recruit multimolecular adhesion complexes to their cytoplasmic domains, which provide structural and mechanosensitive signaling connections between the extracellular and intracellular milieux. The different functions of specific integrin heterodimers, such as α4β1 and α5β1, have been attributed to distinct signal transduction mechanisms that are initiated by selective recruitment of adhesion complex components to integrin cytoplasmic tails. Here, we report the isolation of ligand‐induced adhesion complexes associated with wild‐type α4β1 integrin, an activated α4β1 variant in the absence of the α cytoplasmic domain ( X 4C0), and a chimeric α4β1 variant with α5 leg and cytoplasmic domains (α4 P α5 L ), and the cataloguing of their proteomes by MS . Using hierarchical clustering and interaction network analyses, we detail the differential recruitment of proteins and highlight enrichment patterns of proteins to distinct adhesion complexes. We identify previously unreported components of integrin adhesion complexes and observe receptor‐specific enrichment of molecules with previously reported links to cell migration and cell signaling processes. Furthermore, we demonstrate colocalization of MYO 18 A with active integrin in migrating cells. These datasets provide a resource for future studies of integrin receptor‐specific signaling events.