| First Author | Sato-Nishiuchi R | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 30 | Pages | 25615-30 |
| PubMed ID | 22654117 | Mgi Jnum | J:315946 |
| Mgi Id | MGI:6822382 | Doi | 10.1074/jbc.M112.355016 |
| Citation | Sato-Nishiuchi R, et al. (2012) Polydom/SVEP1 is a ligand for integrin alpha9beta1. J Biol Chem 287(30):25615-30 |
| abstractText | A variety of proteins, including tenascin-C and osteopontin, have been identified as ligands for integrin alpha9beta1. However, their affinities for integrin alpha9beta1 are apparently much lower than those of other integrins (e.g. alpha3beta1, alpha5beta1, and alpha8beta1) for their specific ligands, leaving the possibility that physiological ligands for integrin alpha9beta1 still remain unidentified. In this study, we found that polydom (also named SVEP1) mediates cell adhesion in an integrin alpha9beta1-dependent manner and binds directly to recombinant integrin alpha9beta1 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 alpha9beta1 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 alpha9 in the stomach, intestine, and other organs. Furthermore, in situ integrin alpha9beta1 binding assays using frozen mouse tissues showed that polydom accounts for most, but not all, of the integrin alpha9beta1 ligands in tissues. Taken together, the present findings indicate that polydom is a hitherto unknown ligand for integrin alpha9beta1 that functions as a physiological ligand in vivo. |
