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dc.contributor.authorDimitriadi, Maria
dc.contributor.authorDerdowski, Aaron
dc.contributor.authorKalloo, Geetika
dc.contributor.authorMaginnis, Melissa S
dc.contributor.authorO'Hern, Patrick
dc.contributor.authorBliska, Bryn
dc.contributor.authorSorkaç, Altar
dc.contributor.authorNguyen, Ken C Q
dc.contributor.authorCook, Steven J
dc.contributor.authorPoulogiannis, George
dc.contributor.authorAtwood, Walter J
dc.contributor.authorHall, David H
dc.contributor.authorHart, Anne C
dc.date.accessioned2016-10-26T15:53:53Z
dc.date.available2016-10-26T15:53:53Z
dc.date.issued2016-07-26
dc.identifier.citationDimitriadi , M , Derdowski , A , Kalloo , G , Maginnis , M S , O'Hern , P , Bliska , B , Sorkaç , A , Nguyen , K C Q , Cook , S J , Poulogiannis , G , Atwood , W J , Hall , D H & Hart , A C 2016 , ' Decreased function of survival motor neuron protein impairs endocytic pathways ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 113 , no. 30 , pp. E4377-E4386 . https://doi.org/10.1073/pnas.1600015113
dc.identifier.issn0027-8424
dc.identifier.otherPURE: 10440119
dc.identifier.otherPURE UUID: 638838be-66b3-447b-b8bf-ea5b42f88e9a
dc.identifier.otherPubMed: 27402754
dc.identifier.otherScopus: 84979556428
dc.identifier.urihttp://hdl.handle.net/2299/17279
dc.descriptionThis document is the Accepted Manuscript version. The final, definitive version is available online at https://doi.org/10.1073/pnas.1600015113.
dc.description.abstractSpinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death.en
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.rightsOpen
dc.titleDecreased function of survival motor neuron protein impairs endocytic pathwaysen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionGeography, Environment and Agriculture
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionWeight and Obesity Research Group
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Accepted Version
dcterms.dateAccepted2016-07-26
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1073/pnas.1600015113
rioxxterms.licenseref.uriOther
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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