G protein βγ subunit-mediated presynaptic inhibition:: Regulation of exocytotic fusion downstream of Ca2+ entry
G protein βγ subunit-mediated presynaptic inhibition:: Regulation of exocytotic fusion downstream of Ca2+ entry
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DOI：
10.1126/science.1058803
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发表时间：
2001-04-13
期刊：
影响因子：
56.9
通讯作者：
Hamm, HE
中科院分区：
文献类型：
--
作者：
Blackmer, T;Larsen, EC;Hamm, HE
神经系统可以通过激活异源三聚体GTP结合蛋白(G蛋白)偶联受体的神经递质来调节神经递质的释放。我们发现微量注射G蛋白β-伽马亚基(G-β-γ)可以模拟5-羟色胺对神经传递的抑制作用。释放游离的Gβ伽马对这种作用至关重要，因为Gβ伽马清除剂阻断了5-羟色胺的作用。Gβ伽马对动作电位引起的触发神经传递的快速细胞内钙释放没有影响。在阻断所有经典的Gβ-γ效应通路后，5-羟色胺仍能抑制神经递质的释放。因此，Gβγ阻断了钙离子进入下游的神经递质释放，并可能直接靶向突触前终末的胞吐融合机制。
The nervous system can modulate neurotransmitter release by neurotransmitter activation of heterotrimeric GTP-binding protein (G protein)-coupled receptors. We found that microinjection of G protein beta gamma subunits (G beta gamma) mimics serotonin's inhibitory effect on neurotransmission. Release of free G beta gamma was critical for this effect because a G beta gamma scavenger blocked serotonin's effect. G beta gamma bad no effect on fast, action potential-evoked intracellular Ca2+ release that triggered neurotransmission. Inhibition of neurotransmitter release by serotonin was still seen after blockade of all classical G beta gamma effector pathways. Thus, G beta gamma blocked neurotransmitter release downstream of Ca2+ entry and may directly target the exocytotic fusion machinery at the presynaptic terminal.