The presence of alpha-catenin in the VE-cadherin complex is required for efficient transendothelial migration of leukocytes.
The majority of the leukocytes cross the endothelial lining of the vessels through cell-cell junctions. The junctional protein Vascular Endothelial (VE)-cadherin is transiently re-distributed from sites of cell-cell contacts during passage of leukocytes. VE-cadherin is part of a protein complex comprising p120-catenin and beta-catenin as intracellular partners. Beta-catenin connects VE-cadherin to alpha-catenin. This VE-cadherin-catenin complex is believed to dynamically control endothelial cell-cell junctions and to regulate the passage of leukocytes, although not much is known about the role of alpha- and beta-catenin during the process of transendothelial migration (TEM). In order to study the importance of the interaction between alpha- and beta-catenin in TEM, we used a cell-permeable version of the peptide encoding the binding site of alpha-catenin for beta-catenin (S27D). The data show that S27D interferes with the interaction between alpha- and beta-catenin and induces a reversible decrease in electrical resistance of the endothelial monolayer. In addition, S27D co-localized with beta-catenin at cell-cell junctions. Surprisingly, transmigration of neutrophils across endothelial monolayers was blocked in the presence of S27D. In conclusion, our results show for the first time that the association of alpha-catenin with the cadherin-catenin complex is required for efficient leukocyte TEM.
van Buul
Jaap D
JD
Dept. Molecular Cell Biology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands. j.vanbuul@sanquin.nl
van Alphen
Floris P
FP
Hordijk
Peter L
PL
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D001665:Binding Sites; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D014470:Umbilical Cord; D051178:alpha Catenin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D010455:Peptides; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5; C495270:CTNNB1 protein, human