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Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.

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cam.depositDate2022-05-23
cam.issuedOnline2022-06-13
cam.orpheus.counter1
cam.orpheus.success2022/06/01
dc.contributor.authorDuan, Xiaowen
dc.contributor.authorNorris, Dougall M
dc.contributor.authorHumphrey, Sean J
dc.contributor.authorYang, Pengyi
dc.contributor.authorCooke, Kristen C
dc.contributor.authorBultitude, Will P
dc.contributor.authorParker, Benjamin L
dc.contributor.authorConway, Olivia J
dc.contributor.authorBurchfield, James G
dc.contributor.authorKrycer, James R
dc.contributor.authorBrodsky, Frances M
dc.contributor.authorJames, David E
dc.contributor.authorFazakerley, Daniel J
dc.contributor.orcidFazakerley, Daniel J [0000-0001-8241-2903]
dc.date.accessioned2022-05-24T23:30:12Z
dc.date.available2022-05-24T23:30:12Z
dc.date.issued2022-06-17
dc.date.updated2022-05-23T12:07:24Z
dc.description.abstractTrafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired following Trarg1 knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes.
dc.identifier.doi10.17863/CAM.84850
dc.identifier.eissn1470-8728
dc.identifier.issn0264-6021
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337437
dc.language.isoeng
dc.publisherPortland Press Ltd.
dc.publisher.departmentDepartment of Clinical Biochemistry
dc.publisher.urlhttp://dx.doi.org/10.1042/bcj20220153
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectadipocytes
dc.subjectglucose transport
dc.subjectglycogen synthase kinase
dc.subjectinsulin signalling
dc.subjecttrafficking regulator of GLUT4-1
dc.subjectAdipocytes
dc.subjectAnimals
dc.subjectCell Membrane
dc.subjectGlucose
dc.subjectGlucose Transporter Type 4
dc.subjectGlycogen Synthase Kinase 3
dc.subjectHumans
dc.subjectInsulin
dc.subjectMice
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectPhosphorylation
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectSerine
dc.titleTrafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.
dc.typeArticle
dcterms.dateAccepted2022-05-20
prism.publicationNameBiochem J
pubs.funder-project-idMedical Research Council (MR/S007091/1)
pubs.funder-project-idWellcome Trust (208363/Z/17/Z)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1042/BCJ20220153

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