INDIVIDUAL RESEARCHERPeter A. Vincent , Ph.D.
Education1988 - Ph.D. from Dept. of Physiology, Albany Medical College
Endothelial cells line the wall of all blood vessels, where they play a critical role in a number of physiological responses including regulation of vasoreactivity, hemostasis, and leukocyte recruitment. Vascular endothelial cells also act as a selective barrier that regulates the passage of fluid, macromolecules, and white cells from the vascular space to the interstitium. The proper regulation of fluid and protein flux is critical for maintaining normal tissue function. This is accomplished by a number of transmembrane cell-cell adhesion proteins that, when coupled with their binding partners, contribute to the adhesion of one endothelial cell to another. The adherens junction complex, comprised of cadherins and the catenins, is a major adhesion structure that connects to the actin cytoskeleton. VE-cadherin is found specifically in the endothelial cell adherens junction and has been implicated in playing a fundamental role in controlling the transport across the endothelial barrier and in regulating angiogenesis. The cytoplasmic domain of VE-cadherin binds to β-catenin and plakoglobin, both of which bind to α-catenin, a protein that supports the interaction of the VE-cadherin-catenin complex with the actin cytoskeleton. In addition to catenins, VE-cadherin has been found to interact with other signaling molecules and to serve as a scaffolding molecule that participates in a signaling network that controls endothelial cell-cell adhesion. The research in my laboratory has focused on studying the role of p120 catenin which binds to the juxtamembrane domain of VE-cadherin. Binding of p120 to the JMD region regulates the localization of VE-cadherin to the plasma membrane by inhibiting endocytosis of VE-cadherin. Our research has demonstrated that p120 is critical to maintaining barrier function of the endothelial monolayer and that this is due in part to endocytosis. Ongoing research in the laboratory is trying to determine how p120 regulates endothelial function in addition to regulating endocytosis.
- Alcaide P, Martinelli R, Newton G, Williams MR, Adam A, Vincent PA, Luscinskas FW. p120-Catenin prevents neutrophil transmigration independently of RhoA inhibition by impairing Src dependent VE-cadherin phosphorylation. Am J Physiol Cell Physiol. 2012 Aug;303(4):C385-95. Epub 2012 May 30. PubMed PMID: 22648953.
- Herron CR, Lowery AM, Hollister PR, Reynolds AB, Vincent PA. p120 regulates endothelial permeability independently of its NH2 terminus and Rho binding. Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H36-48. Epub 2010 Oct 22. PubMed PMID: 20971762; PubMed Central PMCID: PMC3023255.
- Zhang J, O'Donnell JJ 3rd, Holian O, Vincent PA, Kim KS, Lum H. P120 catenin represses transcriptional activity through Kaiso in endothelial cells. Microvasc Res. 2010 Sep;80(2):233-9. Epub 2010 Apr 9. PubMed PMID: 20382170; PubMed Central PMCID: PMC2917640.
- Adam AP, Sharenko AL, Pumiglia K, Vincent PA. Src-induced tyrosine phosphorylation of VE-cadherin is not sufficient to decrease barrier function of endothelial monolayers. J Biol Chem. 2010 Mar 5;285(10):7045-55. Epub 2010 Jan 4. PubMed PMID: 20048167; PubMed Central PMCID: PMC2844154