Proteomic analysis of ?4?1 integrin adhesion complexes reveals ?-subunit-dependent protein recruitment.

ABSTRACT: 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 ?4?1 and ?5?1, 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 ?4?1 integrin, an activated ?4?1 variant in the absence of the ? cytoplasmic domain (X4C0), and a chimeric ?4?1 variant with ?5 leg and cytoplasmic domains (?4P?5L), 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 MYO18A with active integrin in migrating cells. These datasets provide a resource for future studies of integrin receptor-specific signaling events.

SUBMITTER: Byron A 

PROVIDER: S-EPMC3472074 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature