dc.contributor.author | Dimitriadi, Maria | |
dc.contributor.author | Derdowski, Aaron | |
dc.contributor.author | Kalloo, Geetika | |
dc.contributor.author | Maginnis, Melissa S | |
dc.contributor.author | O'Hern, Patrick | |
dc.contributor.author | Bliska, Bryn | |
dc.contributor.author | Sorkaç, Altar | |
dc.contributor.author | Nguyen, Ken C Q | |
dc.contributor.author | Cook, Steven J | |
dc.contributor.author | Poulogiannis, George | |
dc.contributor.author | Atwood, Walter J | |
dc.contributor.author | Hall, David H | |
dc.contributor.author | Hart, Anne C | |
dc.date.accessioned | 2016-10-26T15:53:53Z | |
dc.date.available | 2016-10-26T15:53:53Z | |
dc.date.issued | 2016-07-26 | |
dc.identifier.citation | Dimitriadi , 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.issn | 0027-8424 | |
dc.identifier.uri | http://hdl.handle.net/2299/17279 | |
dc.description | This document is the Accepted Manuscript version. The final, definitive version is available online at https://doi.org/10.1073/pnas.1600015113. | |
dc.description.abstract | Spinal 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.extent | 10 | |
dc.format.extent | 2108443 | |
dc.language.iso | eng | |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | |
dc.title | Decreased function of survival motor neuron protein impairs endocytic pathways | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.contributor.institution | Extracellular Vesicle Research Unit | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Future Societies Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1073/pnas.1600015113 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |