Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo

Neuron. 1999 Jul;23(3):593-605. doi: 10.1016/s0896-6273(00)80811-9.


Biochemical studies suggest that syntaxin 1A participates in multiple protein-protein interactions in the synaptic terminal, but the in vivo significance of these interactions is poorly understood. We used a targeted mutagenesis approach to eliminate specific syntaxin binding interactions and demonstrate that Drosophila syntaxin 1A plays multiple regulatory roles in neurotransmission in vivo. Syntaxin mutations that eliminate ROP/Munc-18 binding display increased neurotransmitter release, suggesting that ROP inhibits neurosecretion through its interaction with syntaxin. Syntaxin mutations that block Ca2+ channel binding also cause an increase in neurotransmitter release, suggesting that syntaxin normally functions in inhibiting Ca2+ channel opening. Additionally, we identify and characterize a syntaxin Ca2+ effector domain, which may spatially organize the Ca2+ channel, cysteine string protein, and synaptotagmin for effective excitation-secretion coupling in the presynaptic terminal.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antigens, Surface / chemistry
  • Antigens, Surface / genetics*
  • Antigens, Surface / metabolism*
  • Binding, Competitive / genetics
  • Calcium / metabolism
  • Drosophila
  • Drosophila Proteins*
  • Electrophysiology
  • Exocytosis / physiology*
  • Munc18 Proteins
  • Muscle Contraction
  • Mutagenesis, Site-Directed / physiology
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Protein Structure, Tertiary
  • Synaptic Transmission / genetics
  • Synaptic Vesicles / chemistry
  • Synaptic Vesicles / metabolism
  • Syntaxin 1
  • Vesicular Transport Proteins*


  • Antigens, Surface
  • Drosophila Proteins
  • Munc18 Proteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Rop protein, Drosophila
  • Syntaxin 1
  • Vesicular Transport Proteins
  • Calcium