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

被引:174
作者
Wu, MN
Fergestad, T
Lloyd, TE
He, YC
Broadie, K
Bellen, HJ
机构
[1] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA
[3] Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[5] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
关键词
D O I
10.1016/S0896-6273(00)80811-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:593 / 605
页数:13
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