Premium
REGULATION OF LEUKOCYTE TRANSENDOTHELIAL MIGRATION BY P120 CATENIN/ VASCULAR ENDOTHELIAL‐CADHERIN
Author(s) -
Alcaide Pilar,
Newton Gail,
Sehrawat Seema,
MayadasNorton Tanya,
Luscinskas Francis William
Publication year - 2007
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/fasebj.21.6.lb73
Subject(s) - adherens junction , internalization , microbiology and biotechnology , ve cadherin , cadherin , endocytosis , umbilical vein , endothelial stem cell , biology , endothelium , cell junction , human umbilical vein endothelial cell , catenin , gap junction , chemistry , cell , intracellular , in vitro , signal transduction , wnt signaling pathway , endocrinology , biochemistry
Vascular Endothelial‐cadherin (VE‐Cad) forms the adherens junctions and localizes at endothelial cell‐cell borders, forming a complex with α− β‐ and p120‐catenins that link it to the cytoskeleton. This complex contributes to barrier function and is thought to regulate leukocyte Transendothelial Migration (TEM). p120catenin (p120cat) controls VE‐Cad surface expression in endothelial cells (EC) by regulating its rate of endocytosis and internalization. We previously showed that VE‐Cad transiently and reversible disassociates forming a “gap” at sites of leukocyte TEM under shear flow conditions in vitro. Here we tested the hypothesis that p120cat overexpression in EC prevents VE‐Cad internalization and thus blocks “gap” formation and inhibits TEM. Human Umbilical Vein EC transduced with Adenovirus p120catGFP fusion protein mimicked the behavior of native p120‐cat. By live cell fluorescence microscopy p120catGFP co‐localizes with VE‐Cad and behaves identically, forming gaps at sites of TEM. p120cat overexpression increased VE‐Cad expression 4‐fold and blocked TEM by 50% (x±SD, p<0.05); if cells transmigrated, length of time required was protracted vs control (60s vs 180 sec). We conclude that p120cat is a key regulator of VE‐Cad expression at the junctions, and plays a gatekeeper role in TEM through its effect on regulating the internalization of VE‐Cad.