Defects in synaptic vesicle docking in unc-18 mutants

Nat Neurosci. 2003 Oct;6(10):1023-30. doi: 10.1038/nn1118. Epub 2003 Sep 14.

Abstract

Sec1-related proteins function in most, if not all, membrane trafficking pathways in eukaryotic cells. The Sec1-related protein required in neurons for synaptic vesicle exocytosis is UNC-18. Several models for UNC-18 function during vesicle exocytosis are under consideration. We have tested these models by characterizing unc-18 mutants of the nematode Caenorhabditis elegans. In the absence of UNC-18, the size of the readily releasable pool is severely reduced. Our results show that the near absence of fusion-competent vesicles is not caused by a reduction in syntaxin levels, by a mislocalization of syntaxin, by a defect in fusion or by a failure to open syntaxin during priming. Rather, we found a reduction of docked vesicles at the active zone in unc-18 mutants, suggesting that UNC-18 functions, directly or indirectly, as a facilitator of vesicle docking.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / genetics
  • Electric Stimulation
  • Exocytosis / physiology*
  • Green Fluorescent Proteins
  • Luminescent Proteins
  • Membrane Fusion / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Electron
  • Models, Animal
  • Motor Neurons / cytology
  • Motor Neurons / physiology
  • Mutation / physiology
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / growth & development
  • Neuromuscular Junction / physiology
  • Phosphoproteins*
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Protein Transport / genetics
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • Receptors, GABA / genetics
  • Receptors, GABA / metabolism
  • Recombinant Fusion Proteins
  • Synaptic Transmission / genetics*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Vesicular Transport Proteins*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • Phosphoproteins
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • Receptors, GABA
  • Recombinant Fusion Proteins
  • Unc-18 protein, C elegans
  • Vesicular Transport Proteins
  • Green Fluorescent Proteins
  • gamma-Aminobutyric Acid