Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy
Authors
Oprea, Gabriela E.Krober, Sandra
McWhorter, Michelle L.
Rossoll, Wilfried
Muller, Stefan
Krawczak, Michael
Bassell, Gary J.
Beattie, Christine E.
Wirth, Brunhilde
UMass Chan Affiliations
Department of Cell BiologyInstitute of Human Genetics
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2008-04-29Keywords
Actins; Animals; Axons; Cell Differentiation; Cell Line; Cyclic AMP Response Element-Binding Protein; Female; Gene Expression; Growth Cones; Humans; Male; Membrane Glycoproteins; Mice; Microfilament Proteins; Muscular Atrophy, Spinal; Nerve Tissue Proteins; Pedigree; Phosphoproteins; RNA-Binding Proteins; SMN Complex Proteins; Spinal Cord; Survival of Motor Neuron 1 Protein; Transcription, Genetic; ZebrafishLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Homozygous deletion of the survival motor neuron 1 gene (SMN1) causes spinal muscular atrophy (SMA), the most frequent genetic cause of early childhood lethality. In rare instances, however, individuals are asymptomatic despite carrying the same SMN1 mutations as their affected siblings, thereby suggesting the influence of modifier genes. We discovered that unaffected SMN1-deleted females exhibit significantly higher expression of plastin 3 (PLS3) than their SMA-affected counterparts. We demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish. Our study suggests that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.Source
Science. 2008 Apr 25;320(5875):524-7. Link to article on publisher's siteDOI
10.1126/science.1155085Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32941PubMed ID
18440926Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1126/science.1155085
Scopus Count
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