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VE‐cadherin “gap” formation during transendothelial migration is regulated by a novel mechansim involving the lateral border recycling compartment
Author(s) -
Gonzalez Annette M,
Cyrus Bita,
Muller William A
Publication year - 2013
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.27.1_supplement.57.11
Subject(s) - cadherin , microbiology and biotechnology , phosphorylation , cell junction , ve cadherin , tyrosine , cytoplasm , compartment (ship) , microtubule , gap junction , chemistry , cytoskeleton , intracellular , mutant , cell culture , cell , biology , biochemistry , genetics , oceanography , geology , gene
Leukocyte transendothelial migration (TEM) is regulated by two major events: VE‐cadherin gaps forming at cell‐cell junctions and the lateral border recycling compartment (LBRC) trafficking to the site of transmigration. However, the relationship between these two events is unclear. We previously demonstrated that targeting of the LBRC and subsequent TEM were selectively inhibited by colcemide, a microtubule depolymerizing drug. Using a similar approach, we assessed the role of the LBRC in VE‐cadherin gap formation. VE‐cadherin gap formation was blocked under conditions where targeting of the LBRC was inhibited by colcemide. We obtained similar results using live cell imaging microscopy. Phosphorylation of tyrosine residues Y658 and Y731 on VE‐cadherin's cytoplasmic tail has been shown to be required for transmigration. Mutating these residues to phenylalanine inhibited TEM and formation of VE‐cadherin gaps. We expressed VE‐cadherin double‐mutant (Y658F, Y731F) in endothelial cells and found that targeting of the LBRC still occurred under conditions where VE‐cadherin gaps could not form. Together, these data suggest that targeting of the LBRC to the site of transmigration precedes VE‐cadherin gap formation. We hypothesize that recruitment of the LBRC plays a role in clearing VE‐cadherin from the site of transmigration. Supported by NIH grants RO1 HL046849 and R37 HL064774.