Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1

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dc.contributor.authorRhett, J. Matthewen
dc.contributor.authorJourdan, L. Janeen
dc.contributor.authorGourdie, Robert G.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.coverage.spatialUnited Statesen
dc.date.accessioned2017-02-09T20:20:25Zen
dc.date.available2017-02-09T20:20:25Zen
dc.date.issued2011-05en
dc.description.abstractConnexin 43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular channels comprising GJ aggregates form from docking of paired connexons, with one each contributed by apposing cells. Zonula occludens-1 (ZO-1) binds the carboxy terminus of Cx43, and we have previously shown that inhibition of the Cx43/ZO-1 interaction increases GJ size by 48 h. Here we demonstrated that increases in GJ aggregation occur within 2 h (∼Cx43 half-life) following disruption of Cx43/ZO-1. Immunoprecipitation and Duolink protein-protein interaction assays indicated that inhibition targets ZO-1 binding with Cx43 in GJs as well as connexons in an adjacent domain that we term the "perinexus." Consistent with GJ size increases being matched by decreases in connexons, inhibition of Cx43/ZO-1 reduced the extent of perinexal interaction, increased the proportion of connexons docked in GJs relative to undocked connexons in the plasma membrane, and increased GJ intercellular communication while concomitantly decreasing hemichannel-mediated membrane permeance in contacting, but not noncontacting, cells. ZO-1 small interfering RNA and overexpression experiments verified that loss and gain of ZO-1 function govern the transition of connexons into GJs. It is concluded that ZO-1 regulates the rate of undocked connexon aggregation into GJs, enabling dynamic partitioning of Cx43 channel function between junctional and proximal nonjunctional domains of plasma membrane.en
dc.description.versionPublished versionen
dc.format.extent1516 - 1528 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1091/mbc.E10-06-0548en
dc.identifier.eissn1939-4586en
dc.identifier.issue9en
dc.identifier.urihttp://hdl.handle.net/10919/74986en
dc.identifier.volume22en
dc.language.isoenen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/21411628en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectCell Communicationen
dc.subjectCell Cycleen
dc.subjectCell Membraneen
dc.subjectConnexin 43en
dc.subjectGap Junctionsen
dc.subjectGreen Fluorescent Proteinsen
dc.subjectHeLa Cellsen
dc.subjectHumansen
dc.subjectImmunoprecipitationen
dc.subjectMembrane Proteinsen
dc.subjectPhosphoproteinsen
dc.subjectProtein Bindingen
dc.subjectProtein Interaction Domains and Motifsen
dc.subjectProtein Transporten
dc.subjectRNA Interferenceen
dc.subjectRNA, Small Interferingen
dc.subjectZonula Occludens-1 Proteinen
dc.titleConnexin 43 connexon to gap junction transition is regulated by zonula occludens-1en
dc.title.serialMolecular Biology of the Cellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherResearch Support, N.I.H., Extramuralen
dc.type.otherResearch Support, Non-U.S. Gov'ten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen

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