UNC-13 interaction with syntaxin is required for synaptic transmission

Curr Biol. 2005 Dec 20;15(24):2236-42. doi: 10.1016/j.cub.2005.10.049. Epub 2005 Nov 3.


Neurotransmitter secretion at synapses is controlled by several processes-morphological docking of vesicles at release sites, priming of docked vesicles to make them fusion competent, and calcium-dependent fusion of vesicles with the plasma membrane . In worms, flies, and mice, mutants lacking UNC-13 have defects in vesicle priming . Current models propose that UNC-13 primes vesicles by stabilizing Syntaxin's "open" conformation by directly interacting with its amino-terminal regulatory domain . However, the functional significance of the UNC-13/Syntaxin interaction has not been tested directly. A truncated protein containing the Munc homology domains (MHD1 and MHD2) and the carboxy-terminal C2 domain partially rescued both the behavioral and secretion defects of unc-13 mutants in C. elegans. A double mutation in MHD2 (F1000A/K1002A) disrupts the UNC-13/Syntaxin interaction. The rate of endogenous synaptic events and the amplitude of nerve-evoked excitatory post-synaptic currents (EPSCs) were both significantly reduced in UNC-13S(F1000A/K1002A). However, the pool of primed (i.e., fusion-competent) vesicles was normal. These results suggest that the UNC-13/Syntaxin interaction is conserved in C. elegans and that, contrary to current models, the UNC-13/Syntaxin interaction is required for nerve-evoked vesicle fusion rather than synaptic-vesicle priming. Thus, UNC-13 may regulate multiple steps of the synaptic-vesicle cycle.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins
  • Electrophysiology
  • Molecular Sequence Data
  • Mutation / genetics
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism*
  • Sequence Alignment
  • Sucrose
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Two-Hybrid System Techniques


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Qa-SNARE Proteins
  • phorbol ester binding protein
  • Sucrose