Motorneurons require cysteine string protein-α to maintain the readily releasable vesicular pool and synaptic vesicle recycling

Neuron. 2012 Apr 12;74(1):151-65. doi: 10.1016/j.neuron.2012.02.019.


Cysteine string protein-α (CSP-α) is a synaptic vesicle protein that prevents activity-dependent neurodegeneration by poorly understood mechanisms. We have studied the synaptic vesicle cycle at the motor nerve terminals of CSP-α knock-out mice expressing the synaptopHluorin transgene. Mutant nerve terminals fail to sustain prolonged release and the number of vesicles available to be released decreases. Strikingly, the SNARE protein SNAP-25 is dramatically reduced. In addition, endocytosis during the stimulus fails to maintain the size of the recycling synaptic vesicle pool during prolonged stimulation. Upon depolarization, the styryl dye FM 2-10 becomes trapped and poorly releasable. Consistently with the functional results, electron microscopy analysis revealed characteristic features of impaired synaptic vesicle recycling. The unexpected defect in vesicle recycling in CSP-α knock-out mice provides insights into understanding molecular mechanisms of degeneration in motor nerve terminals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exocytosis / physiology*
  • Green Fluorescent Proteins / metabolism
  • HSP40 Heat-Shock Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Motor Neurons / metabolism*
  • Motor Neurons / ultrastructure
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / ultrastructure
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / ultrastructure
  • Recombinant Fusion Proteins / metabolism
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Synaptosomal-Associated Protein 25 / metabolism


  • HSP40 Heat-Shock Proteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Synaptosomal-Associated Protein 25
  • cysteine string protein
  • synaptopHIuorin
  • Green Fluorescent Proteins