Show simple item record

dc.contributor.authorLeung, Kin-Mei
dc.contributor.authorLu, Bo
dc.contributor.authorWong, Hovy Ho-Wai
dc.contributor.authorLin, Qiaojin
dc.contributor.authorTurner-Bridger, Benita
dc.contributor.authorHolt, Christine
dc.date.accessioned2018-11-17T00:32:04Z
dc.date.available2018-11-17T00:32:04Z
dc.date.issued2018
dc.identifier.issn1662-5102
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285392
dc.description.abstractGuidance cues trigger fast responses in axonal growth cones such as directional turning and collapse that require local protein synthesis. An attractive cue-gradient, such as Netrin-1, triggers de novo synthesis of β-actin localized to the near-side compartment of the growth cone that promotes F-actin assembly and attractive steering. How this precise spatial asymmetry in mRNA translation arises across the small expanse of the growth cone is poorly understood. Pre-localized mRNAs in the vicinity of activated receptors could be selectively translated and/or new mRNAs could be trafficked into the area. Here we have performed live imaging of fluorescent-tagged β-actin mRNA to investigate mRNA trafficking dynamics in Xenopus retinal ganglion cell (RGC) axons and growth cones in response to Netrin-1. A Netrin-1 gradient was found to elicit the transport of β-actin mRNA granules to the near-side of growth cones within a 4-7 min window. This polarized mRNA trafficking depended on the 3' untranslated region (UTR) since mRNA-Δ3'UTR mutant failed to exhibit cue-induced localization. Global application of Netrin-1 significantly increased the anterograde movement of β-actin mRNA along axons and also promoted microtubule-dependent mRNA excursions from the central domain of the growth cone into the periphery (filopodia and lamellipodia). Dual channel imaging revealed β-actin mRNA riding behind the microtubule plus-end tracking protein, EB1, in movements along dynamic microtubules into filopodia. The mRNA-EB1 movements were unchanged by a Netrin-1 gradient indicating the dynamic microtubules themselves do not underlie the cue-induced polarity of RNA movement. Finally, fast-moving elongated "worm-like" trains of Cy3-RNA, distinct from mitochondria, were seen transporting RNA along axons in vitro and in vivo suggesting the existence of a novel transport organelle. Overall, the results provide evidence that the axonal trafficking of β-actin mRNA can be regulated by the guidance cue Netrin-1 to transduce the polarity of an extracellular stimulus and that the 3'UTR is essential for this cue-induced regulation.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherFrontiers Media SA
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCue-Polarized Transport of β-actin mRNA Depends on 3'UTR and Microtubules in Live Growth Cones.
dc.typeArticle
prism.publicationDate2018
prism.publicationNameFront Cell Neurosci
prism.startingPage300
prism.volume12
dc.identifier.doi10.17863/CAM.32758
dcterms.dateAccepted2018-08-17
rioxxterms.versionofrecord10.3389/fncel.2018.00300
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-01
dc.contributor.orcidLin, Qiaojin [0000-0002-2669-6478]
dc.contributor.orcidTurner-Bridger, Benita [0000-0003-3718-3632]
dc.contributor.orcidHolt, Christine [0000-0003-2829-121X]
dc.identifier.eissn1662-5102
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (085314/Z/08/Z)
pubs.funder-project-idEuropean Research Council (322817)
cam.issuedOnline2018-09-10


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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