%0 Journal Article
%T Influence of PECAMŠ\1 ligand interactions on PECAMŠ\1Š\dependent cell motility and filopodia extension
%A Andrew Parambath
%A Debria S. Joe
%A Horace M. DeLisser
%A Valsamma Abraham
%J Archive of "Physiological Reports".
%D 2016
%R 10.14814/phy2.13030
%X Platelet endothelial cell adhesion molecule (PECAMŠ\1) has been implicated in angiogenesis through processes that involve stimulation of endothelial cell motility. Previous studies suggest that PECAMŠ\1 tyrosine phosphorylation mediates the recruitment and then activation of the tyrosine phosphatase SHPŠ\2, which in turn promotes the turnover of focal adhesions and the extension of filopodia, processes critical to cell motility. While these studies have implicated PECAMŠ\1Š\dependent signaling in PECAMŠ\1Š\mediated cell motility, the involvement of PECAMŠ\1 ligand binding in cell migration is undefined. Therefore to investigate the role of PECAMŠ\1 binding interactions in cell motility, mutants of PECAMŠ\1 were generated in which either homophilic or heparin/glycosaminoglycan (GAG)Š\mediated heterophilic binding had been disabled and then expressed in an endothelial cell surrogate. We found that the ability of PECAMŠ\1 to stimulate cell migration, promote filopodia formation and trigger Cdc42 activation were lost if PECAMŠ\1Š\dependent homophilic or heparin/GAGŠ\dependent heterophilic ligand binding was disabled. We further observed that PECAMŠ\1 concentrated at the tips of extended filopodia, an activity that was diminished if homophilic, but not heparin/GAGŠ\mediated heterophilic binding had been disrupted. Similar patterns of activities were seen in mouse endothelial cells treated with antibodies that specifically block PECAMŠ\1Š\dependent homophilic or heterophilic adhesion. Together these data provide evidence for the differential involvement of PECAMŠ\1Š\ligand interactions in PECAMŠ\1Š\dependent motility and the extension of filopodia
%K Cdc42
%K endothelial cells
%K filopodia
%K motility
%K PECAMŠ\1
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358002/