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dc.contributor.authorDimitriadi, M
dc.contributor.authorDerdowski, A
dc.contributor.authorKalloo, G
dc.contributor.authorMaginnis, MS
dc.contributor.authorO'Hern, P
dc.contributor.authorBliska, B
dc.contributor.authorSorkaç, A
dc.contributor.authorNguyen, KCQ
dc.contributor.authorCook, SJ
dc.contributor.authorPoulogiannis, G
dc.contributor.authorAtwood, WJ
dc.contributor.authorHall, DH
dc.contributor.authorHart, AC
dc.date.accessioned2017-04-03T15:47:25Z
dc.date.issued2016-07-11
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2016, 113 (30), pp. E4377 - E4386
dc.identifier.issn0027-8424
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/555
dc.identifier.eissn1091-6490
dc.identifier.doi10.1073/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.
dc.formatPrint-Electronic
dc.format.extentE4377 - E4386
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectMotor Neurons
dc.subjectSynapses
dc.subjectCells, Cultured
dc.subjectAnimals
dc.subjectAnimals, Genetically Modified
dc.subjectHumans
dc.subjectCaenorhabditis elegans
dc.subjectMuscular Atrophy, Spinal
dc.subjectDisease Models, Animal
dc.subjectCaenorhabditis elegans Proteins
dc.subjectSignal Transduction
dc.subjectEndocytosis
dc.subjectRNA Interference
dc.subjectAmino Acid Sequence
dc.subjectSurvival of Motor Neuron 1 Protein
dc.titleDecreased function of survival motor neuron protein impairs endocytic pathways.
dc.typeJournal Article
dcterms.dateAccepted2016-06-02
rioxxterms.versionofrecord10.1073/pnas.1600015113
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-07-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfProceedings of the National Academy of Sciences of the United States of America
pubs.issue30
pubs.notesNo embargo
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.publication-statusPublished
pubs.volume113
pubs.embargo.termsNo embargo
icr.researchteamSignalling & Cancer Metabolismen_US
dc.contributor.icrauthorPoulogiannis, Georgiosen


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