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dc.contributor.authorMartins, Men_US
dc.contributor.authorWarren, Sen_US
dc.contributor.authorKimberley, Cen_US
dc.contributor.authorMargineanu, Aen_US
dc.contributor.authorPeschard, Pen_US
dc.contributor.authorMcCarthy, Aen_US
dc.contributor.authorYeo, Men_US
dc.contributor.authorMarshall, CJen_US
dc.contributor.authorDunsby, Cen_US
dc.contributor.authorFrench, PMWen_US
dc.contributor.authorKatan, Men_US
dc.date.accessioned2018-06-06T09:48:08Z
dc.date.issued2012-12en_US
dc.identifier.citationJournal of cell science, 2012, 125 (Pt 23), pp. 5758 - 5769en_US
dc.identifier.issn0021-9533en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1736
dc.identifier.eissn1477-9137en_US
dc.identifier.doi10.1242/jcs.110007en_US
dc.description.abstractCell chemotaxis, such as migration of fibroblasts towards growth factors during development and wound healing, requires precise spatial coordination of signalling events. Phosphoinositides and signalling enzymes involved in their generation and hydrolysis have been implicated in regulation of chemotaxis; however, the role and importance of specific components remain poorly understood. Here, we demonstrate that phospholipase C epsilon (PLCε) contributes to fibroblast chemotaxis towards platelet-derived growth factor (PDGF-BB). Using PLCe1 null fibroblasts we show that cells deficient in PLCε have greatly reduced directionality towards PDGF-BB without detrimental effect on their basal ability to migrate. Furthermore, we show that in intact fibroblasts, signalling events, such as activation of Rac, are spatially compromised by the absence of PLCε that affects the ability of cells to enlarge their protrusions in the direction of the chemoattractant. By further application of live cell imaging and the use of FRET-based biosensors, we show that generation of Ins(1,4,5)P(3) and recruitment of PLCε are most pronounced in protrusions responding to the PDGF-BB gradient. Furthermore, the phospholipase C activity of PLCε is critical for its role in chemotaxis, consistent with the importance of Ins(1,4,5)P(3) generation and sustained calcium responses in this process. As PLCε has extensive signalling connectivity, using transgenic fibroblasts we ruled out its activation by direct binding to Ras or Rap GTPases, and suggest instead new unexpected links for PLCε in the context of chemotaxis.en_US
dc.formatPrint-Electronicen_US
dc.format.extent5758 - 5769en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectCells, Cultureden_US
dc.subjectFibroblastsen_US
dc.subjectAnimalsen_US
dc.subjectMice, Transgenicen_US
dc.subjectMiceen_US
dc.subjectPlatelet-Derived Growth Factoren_US
dc.subjectChemotaxisen_US
dc.subjectPhosphorylationen_US
dc.subjectPhosphoinositide Phospholipase Cen_US
dc.titleActivity of PLCε contributes to chemotaxis of fibroblasts towards PDGF.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1242/jcs.110007en_US
rioxxterms.licenseref.startdate2012-12en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJournal of cell scienceen_US
pubs.issuePt 23en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene
pubs.publication-statusPublisheden_US
pubs.volume125en_US
pubs.embargo.termsNot knownen_US
pubs.oa-locationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575709/en_US
icr.researchteamOncogeneen_US
dc.contributor.icrauthorMarshall, Christopheren_US


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