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JAM-C induces endothelial cell permeability through its association and regulation of {beta}3 integrins

Li, Xiaochun
Stankovic, Milena
Hahn, Chris N.
Lu, Ying
Vadas, Mathew A.
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Published in Arteriosclerosis, thrombosis, and vascular biology. 2009, vol. 29, no. 8, p. 1200-6
Abstract OBJECTIVE: The molecular mechanisms regulating vascular permeability are only now being elucidated. The junctional adhesion molecule (JAM) JAM-C has been linked to the induction of vascular permeability. We sought to understand the mechanism whereby JAM-C may disrupt junctional integrity in endothelial cells (ECs). METHODS AND RESULTS: We show here that JAM-C alters permeability through modulation of integrin activity. JAM-C overexpression results in an increase in JAM-C at junctions and an increase in permeability. Conversely, knockdown of JAM-C by siRNA results in a reduction in permeability. JAM-C associates with alphavbeta3 integrin and regulates its localization and activity. JAM-C also inhibits the activation state of the beta(1) integrin although it does not associate with this integrin. These changes induced on the integrins are mediated through regulation of the small GTPase, Rap1b but not Rap1a. Thrombin, a powerful inductor of vascular leak, causes localization of JAM-C into the junctions, whereas angiopoietin-1, an inhibitor of permeability, prevents JAM-C translocation. CONCLUSIONS: The regulation of EC junctional integrity involves the coordinated and dynamic modification of localization and activity of junctional stabilizers such as the integrin beta(3) and the destabilizer, JAM-C.
Keywords Adenoviridae/geneticsCapillary Permeability/physiologyCell Adhesion Molecules/biosynthesis/geneticsCell Membrane Permeability/physiologyCells, CulturedEndothelium, Vascular/cytology/metabolismGene Expression RegulationHumansIntegrin beta3/biosynthesis/geneticsRNA, Small Interfering/geneticsTransfectionUmbilical Veins/cytology
PMID: 19461049
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Other version: http://atvb.ahajournals.org/cgi/content/full/29/8/1200
Research group Molécules d'adhésion et processus de migration cellulaire (167)
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LI, Xiaochun et al. JAM-C induces endothelial cell permeability through its association and regulation of {beta}3 integrins. In: Arteriosclerosis, thrombosis, and vascular biology, 2009, vol. 29, n° 8, p. 1200-6. doi: 10.1161/ATVBAHA.109.189217 https://archive-ouverte.unige.ch/unige:5435

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Deposited on : 2010-03-16

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