Recruitment of nectin-3 to cell-cell junctions through trans-heterophilic interaction with CD155, a vitronectin and poliovirus receptor that localizes to alpha(v)beta3 integrin-containing membrane microdomains.
Nectins present a novel class of Ig superfamily adhesion molecules that, cooperatively with cadherins, establish and maintain cell-cell adherens junctions. CD155, the cognate receptor for poliovirus, undergoes cell-matrix contacts by binding to the extracellular matrix protein vitronectin. The significant homology of nectins with CD155 prompted us to investigate the possibility of their interaction. We determined that nectin-3 binds CD155 and its putative mouse homologue Tage4 in cell-based ligand binding assays. Coculture of nectin-3- and CD155-expressing HeLa cells led to CD155-dependent recruitment of nectin-3 to cell-cell contacts. In a heterologous coculture system with CD155 expressing mouse neuroblastoma cells, HeLa cell-expressed nectin-3 was recruited to contact sites with CD155 bearing neurites. CD155 and nectin-3 colocalized to epithelial cell-cell junctions in renal proximal tubules and in the amniotic membrane. Efficient interaction depended on CD155 dimerization, which appears to be aided by cell type-specific cofactors. We furthermore found CD155 to codistribute with alpha(v) integrin microdomains on the surface of transfected mouse fibroblasts and at amniotic epithelial cell junctions. Our findings demonstrate the possible trans-interaction between the bona fide cell-cell adherens type adhesion system (cadherin/nectin) and the cell-matrix adhesion system (integrin/CD155) by virtue of their nectin-3 and CD155 components, respectively.
Mueller
Steffen
S
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794, USA.
Wimmer
Eckard
E
D000650:Amnion / Q000166:cytology; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D019281:Dimerization; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D000075983:Nectins; D009363:Neoplasm Proteins / Q000378:metabolism; D009447:Neuroblastoma; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; D008024:Ligands; D008565:Membrane Proteins; C000619014:NECTIN3 protein, human; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C476587:Taa1 protein, mouse; C066100:poliovirus receptor