Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity. J Cell Sci 2011 May 01;124(Pt 9):1477-85
Date
04/14/2011Pubmed ID
21486942Pubmed Central ID
PMC3078814DOI
10.1242/jcs.082271Scopus ID
2-s2.0-79955525883 (requires institutional sign-in at Scopus site) 91 CitationsAbstract
PECAM-1 (CD31) is a cellular adhesion and signaling receptor that is highly expressed at endothelial cell-cell junctions in confluent vascular beds. Previous studies have implicated PECAM-1 in the maintenance of vascular barrier integrity; however, the mechanisms behind PECAM-1-mediated barrier protection are still poorly understood. The goal of the present study, therefore, was to examine the pertinent biological properties of PECAM-1 (i.e. adhesion and/or signaling) that allow it to support barrier integrity. We found that, compared with PECAM-1-deficient endothelial cells, PECAM-1-expressing endothelial cell monolayers exhibit increased steady-state barrier function, as well as more rapid restoration of barrier integrity following thrombin-induced perturbation of the endothelial cell monolayer. The majority of PECAM-1-mediated barrier protection was found to be due to the ability of PECAM-1 to interact homophilically and become localized to cell-cell junctions, because a homophilic binding-crippled mutant form of PECAM-1 was unable to support efficient barrier function when re-expressed in cells. By contrast, cells expressing PECAM-1 variants lacking residues known to be involved in PECAM-1-mediated signal transduction exhibited normal to near-normal barrier integrity. Taken together, these studies suggest that PECAM-1-PECAM-1 homophilic interactions are more important than its signaling function for maintaining the integrity of endothelial cell junctions.
Author List
Privratsky JR, Paddock CM, Florey O, Newman DK, Muller WA, Newman PJAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinPeter J. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Cell AdhesionCell Line
Endothelial Cells
Humans
Intercellular Junctions
Platelet Endothelial Cell Adhesion Molecule-1
Protein Binding
Signal Transduction
