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dc.contributor.authorTabbasum, Valentina G
dc.contributor.authorCooper, Dermot
dc.date.accessioned2019-02-15T16:10:11Z
dc.date.available2019-02-15T16:10:11Z
dc.date.issued2019-06
dc.identifier.issn0022-2631
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/289457
dc.description.abstractThe fidelity of cAMP in controlling numerous cellular functions rests crucially on the precise organization of cAMP microdomains that are sustained by the scaffolding properties of adenylyl cyclase. Earlier studies suggested that AC8 enriches in lipid rafts where it interacts with cytoskeletal elements. However, these are not stable structures and little is known about the dynamics of AC8 secretion and its interactions. The present study addresses the role of the cytoskeleton in maintaining the AC8 microenvironment, particularly in the context of the trafficking route of AC8 and its interaction with caveolin1. Here, biochemical and live-cell imaging approaches expose a complex, dynamic interaction between AC8 and caveolin1 that affects AC8 processing, targeting and responsiveness in plasma membrane lipid rafts. Site-directed mutagenesis and pharmacological approaches reveal that AC8 is processed with complex N-glycans and associates with lipid rafts en route to the plasma membrane. A dynamic picture emerges of the trafficking and interactions of AC8 while travelling to the plasma membrane, which are key to the organization of the AC8 microdomain.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMembrane Microdomains
dc.subjectCytoskeleton
dc.subjectHumans
dc.subjectBrefeldin A
dc.subjectbeta-Cyclodextrins
dc.subjectGuanine Nucleotide Exchange Factors
dc.subjectBacterial Proteins
dc.subjectLuminescent Proteins
dc.subjectGreen Fluorescent Proteins
dc.subjectRecombinant Fusion Proteins
dc.subjectRNA, Small Interfering
dc.subjectCyclic AMP
dc.subjectMutagenesis, Site-Directed
dc.subjectGene Expression
dc.subjectProtein Transport
dc.subjectGenes, Reporter
dc.subjectCaveolin 1
dc.subjectThiazolidines
dc.subjectHEK293 Cells
dc.subjectAdenylyl Cyclases
dc.subjectBridged Bicyclo Compounds, Heterocyclic
dc.titleStructural and Functional Determinants of AC8 Trafficking, Targeting and Responsiveness in Lipid Raft Microdomains.
dc.typeArticle
prism.endingPage172
prism.issueIdentifier2-3
prism.publicationDate2019
prism.publicationNameJ Membr Biol
prism.startingPage159
prism.volume252
dc.identifier.doi10.17863/CAM.36706
dcterms.dateAccepted2019-01-21
rioxxterms.versionofrecord10.1007/s00232-019-00060-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-06
dc.contributor.orcidCooper, Dermot [0000-0001-5327-5241]
dc.identifier.eissn1432-1424
rioxxterms.typeJournal Article/Review
cam.issuedOnline2019-02-12


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International