DICAM, a novel dual immunoglobulin domain containing cell adhesion molecule interacts with αvβ3 integrin

Immunoglobulin (Ig) superfamily members are abundant with diverse functions including cell adhesion in various tissues. Here, we identified and characterized a novel adhesion molecule that belongs to the CTX protein family and named as DICAM (Dual Ig domain containing cell adhesion molecule). DICAM is a type 1 transmembrane protein with two V-type Ig domains in the extracellular region and a short cytoplasmic tail of 442 amino acids. DICAM is found to be expressed ubiquitously in various organs and cell lines. Subcellular localization of DICAM was observed in the cell-cell contact region and nucleus of cultured epithelial cells. Cell-cell contact region was colocalized with tight junction protein, ZO-1. The DICAM increased MDCK cell adhesion to 60% levels of flbronectin. DICAM mediated cell adhesion was specific for the αvβ3 integrin; other integrins, α2, α5, β1, α2β1, α5β1, were not involved in cell adhesion. In identifying the interacting domain of DICAM with αvβ3, the Ig domain 2 showed higher cell adhesion activity than that of Ig domain 1. Although RGD motif in Ig domain 2 was engaged in cell adhesion, it was not participated in DICAM-αvβ3 mediated cell adhesion. Furthermore, differentially expressing DICAM stable cells showed well correlated cell to cell adhesion capability with integrin β3-overexpressing cells. Collectively, these results indicate that DICAM, a novel dual Ig domain containing adhesion molecule, mediates cell adhesion via αvβ3 integrin.