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dc.contributor.authorHampson, Elizabeth
dc.contributor.authorTsonou, Elpida
dc.contributor.authorBaker, Martin J
dc.contributor.authorHornigold, David C
dc.contributor.authorHubbard, Roderick E
dc.contributor.authorMassey, Andrew
dc.contributor.authorWelch, Heidi Christine Erika
dc.date.accessioned2021-12-03T00:30:28Z
dc.date.available2021-12-03T00:30:28Z
dc.date.issued2021-09-18
dc.identifier.issn2073-4409
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331221
dc.description.abstractP-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates Rac-type small G proteins in response to the stimulation of a range of receptors, particularly G protein-coupled receptors (GPCRs), to control cytoskeletal dynamics and other Rac-dependent cell responses. P-Rex1 is mainly expressed in leukocytes and neurons. Whereas its roles in leukocytes have been studied extensively, relatively little is known about its functions in neurons. Here, we used CRISPR/Cas9-mediated P-Rex1 deficiency in neuronal PC12 cells that stably overexpress the GPCR S1PR1, a receptor for sphingosine 1-phosphate (S1P), to investigate the role of P-Rex1 in neuronal GPCR signalling and cell responses. We show that P-Rex1 is required for the S1P-stimulated activation of Rac1 and Akt, basal Rac3 activity, and constitutive cAMP production in PC12-S1PR1 cells. The constitutive cAMP production was not due to increased expression levels of major neuronal adenylyl cyclases, suggesting that P-Rex1 may regulate adenylyl cyclase activity. P-Rex1 was required for maintenance of neurite protrusions and spreading in S1P-stimulated PC12-S1PR1 cells, as well as for cell-cycle progression and proliferation. In summary, we identified novel functional roles of P-Rex1 in neuronal Rac, Akt and cAMP signalling, as well as in neuronal cell-cycle progression and proliferation.
dc.format.mediumElectronic
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectG protein-coupled receptor (GPCR)
dc.subjectGEF
dc.subjectP-Rex1
dc.subjectRac1
dc.subjectRac3
dc.subjectRho GTPase
dc.subjectcell morphology
dc.subjectcell proliferation
dc.subjectcell-cycle progression
dc.subjectguanine-nucleotide exchange factor
dc.subjectneuronal signalling
dc.subjectAnimals
dc.subjectCell Cycle
dc.subjectCell Movement
dc.subjectCell Proliferation
dc.subjectGuanine Nucleotide Exchange Factors
dc.subjectLysophospholipids
dc.subjectNeurites
dc.subjectNeurons
dc.subjectPC12 Cells
dc.subjectRats
dc.subjectSignal Transduction
dc.subjectSphingosine
dc.subjectSphingosine-1-Phosphate Receptors
dc.subjectrac GTP-Binding Proteins
dc.subjectrac1 GTP-Binding Protein
dc.titleP-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells.
dc.typeArticle
dc.publisher.departmentBabraham Institute
dc.date.updated2021-12-02T09:55:19Z
prism.endingPage2474
prism.issueIdentifier9
prism.numberARTN 2474
prism.publicationDate2021
prism.publicationNameCells
prism.startingPage2474
prism.volume10
dc.identifier.doi10.17863/CAM.78666
dcterms.dateAccepted2021-09-15
rioxxterms.versionofrecord10.3390/cells10092474
rioxxterms.versionVoR
dc.contributor.orcidBaker, Martin J [0000-0002-9743-6294]
dc.contributor.orcidHornigold, David C [0000-0002-3354-2768]
dc.contributor.orcidWelch, Heidi Christine Erika [0000-0001-7865-7000]
dc.identifier.eissn2073-4409
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-09-18
cam.depositDate2021-12-02
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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