Ligand binding in PECAM‐1‐dependent cell motility (832.8)

Although PECAM‐1 is able to mediate homophilic or heterophilic ligand binding, the roles of these interactions in PECAM‐1‐dependent cell motility have not been determined. Mutants of mouse PECAM‐1 (MP) in which homophilic (MPΔHom) or heterophilic (MPΔHet) binding are disabled by targeted mutations in the extracellular domain of the molecule were generated and expressed in REN cells (an endothelial cell surrogate). The resulting cells, along with wild type controls, were assessed for localization at intercellular junctions and wound‐induced tyrosine phosphorylation (required for PECAM‐1 dependent cell motility), cell migration and filopodia formation. Our findings are summarized in the table.Construct Localization to Intercellular Junctions Wound‐Induced Tyrosine Phosphorylation Increased Wound‐Induced Migration Increased Filopodia FormationWild type Yes Yes Yes Yes MPΔHom No Yes No No MPΔHet Yes Yes No NoAs expected, disabling homophilic (but not heterophilic) adhesion prevented the localization of PECAM‐1 at intercellular junctions. Further, despite preservation of tyrosine phosphorylation, loss of either homophilic or heterophilic binding completely eliminated the increases in wound‐induced migration and filopodia formation resulting from the expression of PECAM‐1. These data therefore suggest that in the setting of PECAM‐1‐dependent cell motility, ligand interactions occur downstream of PECAM‐1 tyrosine phosphorylation and that both homophilic and heterophilic binding are necessary for the increase in cell motility and filopodia formation mediated by PECAM‐1. Thus during PECAM‐1‐dependent cell motility, PECAM‐1‐PECAM‐1 interactions in the membrane, as well as PECAM‐1‐matrix interactions may be active. Grant Funding Source : Supported by VA Merit Award