title: Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo.
abstract: 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.
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Wu
authors.forename: T
authors.initials: T
authors.lastname: Fergestad
authors.forename: T E
authors.initials: TE
authors.lastname: Lloyd
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.forename: K
authors.initials: K
authors.lastname: Broadie
authors.forename: H J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: 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
chemical_list: 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