The COPI vesicle complex binds and moves with survival motor neuron within axons

Hum Mol Genet. 2011 May 1;20(9):1701-11. doi: 10.1093/hmg/ddr046. Epub 2011 Feb 7.


Spinal muscular atrophy (SMA), an inherited disease of motor neuron dysfunction, results from insufficient levels of the survival motor neuron (SMN) protein. Movement of the SMN protein as granules within cultured axons suggests that the pathogenesis of SMA may involve defects in neuronal transport, yet the nature of axon transport vesicles remains enigmatic. Here we show that SMN directly binds to the α-subunit of the coat protein I (COPI) vesicle coat protein. The α-COP protein co-immunoprecipitates with SMN, small nuclear ribonucleoprotein-associated assembly factors and β-actin mRNA. Although typically Golgi associated, in neuronal cells α-COP localizes to lamellipodia and growth cones and moves within the axon, with a subset of these granules traveling together with SMN. Depletion of α-COP resulted in mislocalization of SMN and actin at the leading edge at the lamellipodia. We propose that neurons utilize the Golgi-associated COPI vesicle to deliver cargoes necessary for motor neuron integrity and function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Cell Line
  • Cell Survival
  • Coat Protein Complex I / genetics
  • Coat Protein Complex I / metabolism*
  • Disease Models, Animal
  • Humans
  • Mice
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism*
  • Protein Binding
  • Protein Transport
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 1 Protein / metabolism
  • Transport Vesicles / genetics
  • Transport Vesicles / metabolism*


  • Coat Protein Complex I
  • SMN1 protein, human
  • Smn1 protein, mouse
  • Survival of Motor Neuron 1 Protein