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dc.contributor.authorCioni, Jean-Michelen
dc.contributor.authorLin, Qiaojinen
dc.contributor.authorHoltermann, Anne Ven
dc.contributor.authorKoppers, Maxen
dc.contributor.authorJakobs, Maximilianen
dc.contributor.authorAzizi, Afnanen
dc.contributor.authorTurner-Bridger, Benitaen
dc.contributor.authorShigeoka, Toshiakien
dc.contributor.authorFranze, Kristianen
dc.contributor.authorHarris, Williamen
dc.contributor.authorHolt, Christineen
dc.date.accessioned2018-12-18T00:33:17Z
dc.date.available2018-12-18T00:33:17Z
dc.date.issued2019-01-03en
dc.identifier.issn0092-8674
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287127
dc.description.abstractLocal translation regulates the axonal proteome, playing an important role in neuronal wiring and axon maintenance. How axonal mRNAs are localized to specific subcellular sites for translation, however, is not understood. Here, we report that RNA granules associate with endosomes along the axons of retinal ganglion cells. RNA-bearing Rab7a-late endosomes also associate with ribosomes, and real-time translation imaging reveals that they are sites of local protein synthesis. We show that RNA-bearing late endosomes often pause on mitochondria and that mRNAs encoding proteins for mitochondrial function are translated on Rab7a-endosomes. Disruption of Rab7a function with Rab7a mutants, including those associated with Charcot-Marie-Tooth type 2B neuropathy, markedly decreases axonal protein synthesis, impairs mitochondrial function and compromises axonal viability. Our findings thus reveal that late endosomes interact with RNA granules, translation machinery and mitochondria, and suggest that they serve as sites for regulating the supply of nascent pro-survival proteins in axons.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.subjectAxonsen
dc.subjectRetinal Ganglion Cellsen
dc.subjectEndosomesen
dc.subjectMitochondriaen
dc.subjectRibosomesen
dc.subjectAnimalsen
dc.subjectXenopus laevisen
dc.subjectrab GTP-Binding Proteinsen
dc.subjectXenopus Proteinsen
dc.subjectRNAen
dc.subjectRNA, Messengeren
dc.subjectProtein Biosynthesisen
dc.titleLate Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.en
dc.typeArticle
prism.endingPage72.e15
prism.issueIdentifier1-2en
prism.publicationDate2019en
prism.publicationNameCellen
prism.startingPage56
prism.volume176en
dc.identifier.doi10.17863/CAM.34436
dcterms.dateAccepted2018-11-18en
rioxxterms.versionofrecord10.1016/j.cell.2018.11.030en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-01-03en
dc.contributor.orcidCioni, Jean-Michel [0000-0002-8651-5579]
dc.contributor.orcidLin, Qiaojin [0000-0002-2669-6478]
dc.contributor.orcidKoppers, Max [0000-0002-7751-1082]
dc.contributor.orcidJakobs, Maximilian [0000-0002-0879-7937]
dc.contributor.orcidAzizi, Afnan [0000-0002-3288-9612]
dc.contributor.orcidTurner-Bridger, Benita [0000-0003-3718-3632]
dc.contributor.orcidFranze, Kristian [0000-0002-8425-7297]
dc.contributor.orcidHarris, William [0000-0002-9995-8096]
dc.contributor.orcidHolt, Christine [0000-0003-2829-121X]
dc.identifier.eissn1097-4172
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (085314/Z/08/Z)
pubs.funder-project-idEuropean Research Council (322817)
pubs.funder-project-idWellcome Trust (203249/Z/16/Z)
pubs.funder-project-idWellcome Trust (100329/Z/12/Z)
pubs.funder-project-idBBSRC (BB/N006402/1)
rioxxterms.freetoread.startdate2020-01-10


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