p120-catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation

Pilar Alcaide, Gail Newton, Scott Auerbach, Seema Sehrawat, Tanya N. Mayadas, David E. Golan, Patrick Yacono, Peter Vincent, Andrew Kowalczyk, Francis W. Luscinskas

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Vascular endothelial-cadherin (VE-cad) is localized to adherens junctions at endothelial cell borders and forms a complex with α-, β-, γ-, and p120-catenins (p120). We previously showed that the VE-cad complex disassociates to form shortlived "gaps" during leukocyte transendothelial migration (TEM); however, whether these gaps are required for leukocyte TEM is not clear. Recently p120 has been shown to control VE-cad surface expression through endocytosis. We hypothesized that p120 regulates VE-cad surface expression, which would in turn have functional consequences for leukocyte transmigration. Here we show that endothelial cells transduced with an adenovirus expressing p120GFP fusion protein significantly increase VE-cad expression. Moreover, endothelial junctions with high p120GFP expression largely prevent VE-cad gap formation and neutrophil leukocyte TEM; if TEM occurs, the length of time required is prolonged. We find no evidence that VE-cad endocytosis plays a role in VE-cad gap formation and instead show that this process is regulated by changes in VE-cad phosphorylation. In fact, a nonphosphorylatable VE-cad mutant prevented TEM. In summary, our studies provide compelling evidence that VE-cad gap formation is required for leukocyte transmigration and identify p120 as a critical intracellular mediator of this process through its regulation of VE-cad expression at junctions.

Original languageEnglish (US)
Pages (from-to)2770-2779
Number of pages10
JournalBlood
Volume112
Issue number7
DOIs
StatePublished - Oct 1 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint

Dive into the research topics of 'p120-catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation'. Together they form a unique fingerprint.

Cite this