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dc.contributor.authorKitchen, P
dc.contributor.authorÖberg, F
dc.contributor.authorSjöhamn, J
dc.contributor.authorHedfalk, K
dc.contributor.authorBill, RM
dc.contributor.authorTörnroth-Horsefield, S
dc.contributor.authorConner, Matthew T.
dc.contributor.authorConner, Alex C.
dc.date.accessioned2019-05-13T10:40:51Z
dc.date.available2019-05-13T10:40:51Z
dc.date.issued2015-11-16
dc.identifier.citationKitchen P., Öberg F., Sjöhamn J., Hedfalk K., Bill R. M., Conner A. C., et al. (2015) Plasma membrane abundance of human Aquaporin 5 Is dynamically regulated by multiple pathways. PLoS ONE 10(11): e0143027. doi:10.1371/journal.pone.0143027.en
dc.identifier.pmid26569106
dc.identifier.doi10.1371/journal.pone.0143027en
dc.identifier.urihttp://hdl.handle.net/2436/622344
dc.description.abstract© 2015 Kitchen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Aquaporin membrane protein channels mediate cellular water flow. Human aquaporin 5 (AQP5) is highly expressed in the respiratory system and secretory glands where it facilitates the osmotically-driven generation of pulmonary secretions, saliva, sweat and tears. Dysfunctional trafficking of AQP5 has been implicated in several human disease states, including Sjögren's syndrome, bronchitis and cystic fibrosis. In order to investigate how the plasma membrane expression levels of AQP5 are regulated, we studied real-time translocation of GFP-tagged AQP5 in HEK293 cells. We show that AQP5 plasma membrane abundance in transfected HEK293 cells is rapidly and reversibly regulated by at least three independent mechanisms involving phosphorylation at Ser156, protein kinase A activity and extracellular tonicity. The crystal structure of a Ser156 phosphomimetic mutant indicates that its involvement in regulating AQP5 membrane abundance is not mediated by a conformational change of the carboxy-terminus. We suggest that together these pathways regulate cellular water flow.en
dc.description.sponsorshipThis work was supported by the Swedish Research Council (www.vr.se) grants 2009-360 and 2010-5208 (to STH), European Commission Framework Programme 7 (http://ec.europa.eu/research/fp7/index_en.cfm) Grant 201924 EDICT (to RMB) and by the Engineering and Physical Sciences Research Council (https://www.epsrc.ac.uk) through the Molecular Organisation and Assembly in Cells Doctoral Training Centre, University of Warwick, grant number EP/F500378/1 (PK).en
dc.formatapplication/PDFen
dc.languageeng
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
dc.relation.urlhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143027en
dc.rightsLicence for published version: Creative Commons Attribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Membraneen
dc.subjectHumansen
dc.subjectCyclic AMP-Dependent Protein Kinasesen
dc.subjectSerineen
dc.subjectHypotonic Solutionsen
dc.subjectProtein Kinase Inhibitorsen
dc.subjectCrystallography, X-Rayen
dc.subjectSignal Transductionen
dc.subjectProtein Structure, Secondaryen
dc.subjectProtein Transporten
dc.subjectPhosphorylationen
dc.subjectMutationen
dc.subjectModels, Molecularen
dc.subjectMutant Proteinsen
dc.subjectAquaporin 5en
dc.subjectHEK293 Cellsen
dc.titlePlasma membrane abundance of human aquaporin 5 is dynamically regulated by multiple pathwaysen
dc.typeJournal articleen
dc.identifier.eissn1932-6203
dc.identifier.journalPLoS ONEen
dc.date.updated2019-05-09T13:34:00Z
dc.contributor.institutionMolecular Organization and Assembly in Cells Doctoral Training Centre, University of Warwick, Coventry, United Kingdom.
dc.identifier.articlenumbere0143027
pubs.place-of-publicationUnited States
dc.date.accepted2015-10-29
rioxxterms.funderJiscen
rioxxterms.identifier.project1091578en
rioxxterms.versionAOen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2019-05-13en
dc.source.volume10
dc.source.issue11
dc.description.versionPublished version
refterms.dateFOA2019-05-13T10:40:51Z


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Licence for published version: Creative Commons Attribution 4.0 International
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International