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dc.contributor.authorAmsellem, Valerieen_US
dc.contributor.authorDryden, Nicola Hen_US
dc.contributor.authorMartinelli, Robertaen_US
dc.contributor.authorGavins, Felicityen_US
dc.contributor.authorAlmagro, Lourdes Osunaen_US
dc.contributor.authorBirdsey, Graeme Men_US
dc.contributor.authorHaskard, Dorian Oen_US
dc.contributor.authorMason, Justin Cen_US
dc.contributor.authorTurowski, Patricen_US
dc.contributor.authorRandi, Anna Men_US
dc.date.accessioned2014-07-07T18:14:13Z
dc.date.issued2014en_US
dc.identifier.citationAmsellem, Valerie, Nicola H Dryden, Roberta Martinelli, Felicity Gavins, Lourdes Osuna Almagro, Graeme M Birdsey, Dorian O Haskard, Justin C Mason, Patric Turowski, and Anna M Randi. 2014. “ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling.” Cell Communication and Signaling : CCS 12 (1): 12. doi:10.1186/1478-811X-12-12. http://dx.doi.org/10.1186/1478-811X-12-12.en
dc.identifier.issn1478-811Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12406924
dc.description.abstractBackground: Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis. Results: In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ΔERM) or the cytoplasmic tail (IC2 ΔTAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls. Conclusions: These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1478-811X-12-12en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015342/pdf/en
dash.licenseLAAen_US
dc.subjectEndothelialen
dc.subjectICAM-2en
dc.subjectN-Cadherinen
dc.subjectERMen
dc.subjectRac-1en
dc.subjectCell adhesionen
dc.subjectPermeabilityen
dc.subjectCell-cell junctionsen
dc.titleICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signallingen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalCell Communication and Signaling : CCSen
dash.depositing.authorMartinelli, Robertaen_US
dc.date.available2014-07-07T18:14:13Z
dc.identifier.doi10.1186/1478-811X-12-12*
dash.contributor.affiliatedMartinelli, Roberta


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