Polydom/SVEP1 is a ligand for integrin ?9?1.

ABSTRACT: A variety of proteins, including tenascin-C and osteopontin, have been identified as ligands for integrin ?9?1. However, their affinities for integrin ?9?1 are apparently much lower than those of other integrins (e.g. ?3?1, ?5?1, and ?8?1) for their specific ligands, leaving the possibility that physiological ligands for integrin ?9?1 still remain unidentified. In this study, we found that polydom (also named SVEP1) mediates cell adhesion in an integrin ?9?1-dependent manner and binds directly to recombinant integrin ?9?1 with an affinity that far exceeds those of the known ligands. Using a series of recombinant polydom proteins with N-terminal deletions, we mapped the integrin-binding site to the 21st complement control protein domain. Alanine-scanning mutagenesis revealed that the EDDMMEVPY sequence (amino acids 2636-2644) in the 21st complement control protein domain was involved in the binding to integrin ?9?1 and that Glu(2641) was the critical acidic residue for the integrin binding. The importance of this sequence was further confirmed by integrin binding inhibition assays using synthetic peptides. Immunohistochemical analyses of mouse embryonic tissues showed that polydom colocalized with integrin ?9 in the stomach, intestine, and other organs. Furthermore, in situ integrin ?9?1 binding assays using frozen mouse tissues showed that polydom accounts for most, but not all, of the integrin ?9?1 ligands in tissues. Taken together, the present findings indicate that polydom is a hitherto unknown ligand for integrin ?9?1 that functions as a physiological ligand in vivo.

SUBMITTER: Sato-Nishiuchi R 

PROVIDER: S-EPMC3408197 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature