Mutant dynactin in motor neuron disease

Nat Genet. 2003 Apr;33(4):455-6. doi: 10.1038/ng1123. Epub 2003 Mar 10.


Impaired axonal transport in motor neurons has been proposed as a mechanism for neuronal degeneration in motor neuron disease. Here we show linkage of a lower motor neuron disease to a region of 4 Mb at chromosome 2p13. Mutation analysis of a gene in this interval that encodes the largest subunit of the axonal transport protein dynactin showed a single base-pair change resulting in an amino-acid substitution that is predicted to distort the folding of dynactin's microtubule-binding domain. Binding assays show decreased binding of the mutant protein to microtubules. Our results show that dysfunction of dynactin-mediated transport can lead to human motor neuron disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Biological Transport
  • Centromere / metabolism
  • Chromosomes, Human, Pair 2*
  • Cloning, Molecular
  • Drosophila
  • Dynactin Complex
  • Genetic Linkage
  • Humans
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics*
  • Microtubules / metabolism
  • Models, Genetic
  • Models, Molecular
  • Motor Neuron Disease / genetics*
  • Mutation
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Transport
  • Recombination, Genetic


  • Dynactin Complex
  • Microtubule-Associated Proteins