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PECAM‐1 (CD31) engagement activates a phosphoinositide‐independent, nonspecific cation channel in endothelial cells
Author(s) -
O'Brien Christopher D.,
Ji Guangju,
Xiao Wang Yong,
Sun Jing,
Krymskaya Vera P.,
Ruberg Frederick L.,
Kotlikoff Michael I.,
Albelda Steven M.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0467fje
Subject(s) - cd31 , chemistry , microbiology and biotechnology , channel (broadcasting) , biophysics , biology , biochemistry , computer science , telecommunications , in vitro
Platelet endothelial cell adhesion molecule‐1 (PECAM‐1) has been found to modulate a range of endothelial processes, including leukocyte transmigration, angiogenesis, migration, and monolayer permeability through unknown signaling mechanisms. Previous studies have shown that antibody engagement of PECAM‐1 yields prolonged calcium transients in human umbilical vein endothelial cells (HUVEC) and in REN cells, an endothelia‐like mesothelioma‐derived cell line, stably transfected with PECAM‐1 (RHP cells). To define the mechanisms underlying PECAM‐1‐dependent calcium transients in endothelial cells, patch clamp experiments were conducted in HUVEC and in REN cells stably transfected with wild‐type and mutant PECAM‐1. Engagement of PECAM‐1 with monoclonal antibodies, Fab fragments, and a soluble PECAM‐1/Ig homophilic ligand elicited a prolonged inward current, inhibited by genistein, which required an intact PECAM‐1 cytoplasmic domain and Src kinase activity. The channel mediating this PECAM‐1‐dependent current is a calcium‐permeant, voltage‐independent, nonselective cation (NSC) channel with kinetics similar to store‐operated or depletion‐activated channels that mediate capacitative calcium entry in endothelial cells. However, PECAM‐1‐dependent current activation was independent of IP 3 ‐gated Ca +2 store release, phosphoinositide turnover, or intracellular calcium elevation. This PECAM‐1‐regulated current represents a novel calcium signaling pathway that may play a significant role in the range of endothelial physiologic processes, such as neutrophil transmigration, that are modulated by PECAM‐1.