GSBS Student Publications


Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy

UMMS Affiliation

Graduate School of Biomedical Sciences; Institute of Human Genetics; Department of Cell Biology



Document Type


Medical Subject Headings

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; Zebrafish


Life Sciences | Medicine and Health Sciences


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.

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Citation: Science. 2008 Apr 25;320(5875):524-7. Link to article on publisher's site

DOI of Published Version


Related Resources

Link to Article in PubMed

Journal Title

Science (New York, N.Y.)

PubMed ID