Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo.
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.
Wu
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MN
Department of Cell Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Fergestad
T
T
Lloyd
T E
TE
He
Y
Y
Broadie
K
K
Bellen
H J
HJ
D000818:Animals; D030801:Animals, Genetically Modified; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001667:Binding, Competitive / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D004594:Electrophysiology; D005089:Exocytosis / Q000502:physiology*; D051938:Munc18 Proteins; D009119:Muscle Contraction; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D029721:Drosophila Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C086393:Rop protein, Drosophila; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D002118:Calcium