First published online December 20, 2007
Journal of Cell Science 121, 105e (2008)
© The Company of Biologists Limited
ICAM, I saw, I crossed
To reach sites of inflammation, lymphocytes must leave the blood and cross the vascular endothelium. They first dock on intercellular adhesion molecule 1 (ICAM1) on endothelial cells and, subsequently, traverse the cell barrier, aided by the disengagement and reforming of intercellular junctions. The signalling pathways that link ICAM1 docking to reorganisation of junctions are not clearly understood. On page 29, Patric Turowski and colleagues demonstrate that lymphocyte docking (or activation of ICAM1 by antibody binding) leads to tyrosine phosphorylation of the intracellular domain of vascular endothelial cadherin (VEC), an adherens junction protein, but not of other junction proteins. Turowski et al. go on to generate single phenylalanine mutants of three conserved tyrosine residues in VEC. They demonstrate that transendothelial migration is decreased by overexpression of the mutants, although docking is unaffected. Furthermore, phosphorylation of VEC increases permeability of the endothelial monolayer to dextran. These findings suggest that VEC phosphorylation mediates the reorganisation of adherens junctions and thereby promotes the migration of lymphocytes through the endothelial cell barrier.
Related articles in JCS:
- Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration
- Patric Turowski, Roberta Martinelli, Rebecca Crawford, David Wateridge, Anna-Pia Papageorgiou, Maria Grazia Lampugnani, Alexander C. Gamp, Dietmar Vestweber, Peter Adamson, Elisabetta Dejana, and John Greenwood
JCS 2008 121: 29-37.
[Abstract]
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