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dc.contributor.authorBrandstaetter, Hemmaen
dc.contributor.authorKruppa, Antoninaen
dc.contributor.authorBuss, Folmaen
dc.date.accessioned2015-02-10T15:52:09Z
dc.date.available2015-02-10T15:52:09Z
dc.date.issued2014-10-31en
dc.identifier.citationDisease Models & Mechanisms (2014) 7, 1335-1340. doi:10.124. DOI: 10.1242/dmm.017368en
dc.identifier.issn1754-8403
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246722
dc.description.abstractHuntingtin is a large membrane associated scaffolding protein that associates with endocytic and exocytic vesicles and modulates their trafficking along cytoskeletal tracks. Although Huntington's disease progression is linked to toxic accumulation of mutant huntingtin protein, loss of wildtype huntingtin function may also contribute to neuronal cell death but its precise function is not well understood. Therefore, we investigated the molecular role of huntingtin in exocytosis and observed that huntingtin knockdown in HeLa cells causes a delay in ER-to-Golgi transport and a reduction in the number of cargo vesicles leaving the trans-Golgi network. In addition, huntingtin is required for secretory vesicle fusion at the plasma membrane. Similar defects in the early exocytic pathway were observed in primary fibroblasts from homozygous Q140 huntingtin knock-in mice that lack wildtype huntingtin expression. Interestingly, heterozygous fibroblasts from a Huntington’s disease patient with a Q180 expansion displayed no obvious defects in the early secretory pathway. Thus, our results highlight the requirement for wildtype huntingtin at distinct steps along the secretory pathway.
dc.description.sponsorshipThis work was supported by the Cure Huntingtin’s Disease Initiative (CHDI) (H.B. and A.J.K.), the Wellcome Trust (grant number 086743 to F.B.) and the Medical Research Council (grant number MR/K000888/1 to F.B). The CIMR is in receipt of a strategic award from the Wellcome Trust (grant number 100140).
dc.languageEnglishen
dc.language.isoenen
dc.publisherThe Company of Biologists
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectExocytosisen
dc.subjecthuntingtinen
dc.subjectERen
dc.subjectGolgien
dc.subjectvesicle fusionen
dc.titleHuntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion at the plasma membraneen
dc.typeArticle
dc.description.versionThis is the accepted manuscript. It first appeared at http://dmm.biologists.org/content/early/2014/10/30/dmm.017368.en
prism.endingPage1340
prism.publicationDate2014en
prism.publicationNameDisease Models & Mechanismsen
prism.startingPage1335
prism.volume7en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderMRC
dc.rioxxterms.projectid086743
dc.rioxxterms.projectidMR/K000888/1
dc.rioxxterms.projectid100140
rioxxterms.versionofrecord10.1242/dmm.017368en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-10-31en
dc.contributor.orcidBuss, Folma [0000-0003-4457-3479]
dc.identifier.eissn1754-8411
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/K001981/1)
pubs.funder-project-idMRC (MR/K000888/1)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (086743/Z/08/Z)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales