PUBLICATION

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

Authors
Oprea, G.E., Kröber, S., McWhorter, M.L., Rossoll, W., Müller, S., Krawczak, M., Bassell, G.J., Beattie, C.E., and Wirth, B.
ID
ZDB-PUB-080429-13
Date
2008
Source
Science (New York, N.Y.)   320(5875): 524-527 (Journal)
Registered Authors
Beattie, Christine, McWhorter, Michelle
Keywords
none
MeSH Terms
  • Actins/blood
  • Actins/genetics*
  • Actins/metabolism*
  • Animals
  • Axons/metabolism
  • Axons/physiology*
  • Axons/ultrastructure
  • Cell Differentiation
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein/genetics
  • Cyclic AMP Response Element-Binding Protein/metabolism
  • Female
  • Gene Expression
  • Growth Cones/metabolism
  • Growth Cones/ultrastructure
  • Humans
  • Male
  • Membrane Glycoproteins
  • Mice
  • Microfilament Proteins
  • Muscular Atrophy, Spinal/genetics*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Pedigree
  • Phosphoproteins/blood
  • Phosphoproteins/genetics*
  • Phosphoproteins/metabolism*
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism
  • SMN Complex Proteins
  • Spinal Cord/metabolism
  • Survival of Motor Neuron 1 Protein
  • Transcription, Genetic
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed
18440926 Full text @ Science
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes