PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter.

PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter.
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DOI:
10.1083/jcb.200504055
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发表时间:
2005-09-26
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Takai Y
Takai Y
中科院分区:
其他
文献类型:
--
作者:
Baba T;Sakisaka T;Mochida S;Takai Y

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神经递质是通过Ca2+依赖性胞吐作用从神经末梢释放的。SNARE蛋白是启动和融合步骤的关键成分,启动步骤由camp依赖性蛋白激酶(PKA)调节,导致突触可塑性。我们发现SNARE调节蛋白tomosyn被PKA直接磷酸化,这减少了它与syntaxin-1 (SNAREs的一个组成部分)的相互作用,并增强了SNARE复合物的形成。利用培养的上颈神经节(SCG)神经元进行的电生理研究表明,pka催化的tomosyn磷酸化增加了SNARE复合物的形成,增加了突触囊泡的融合能力,从而增加了神经递质的释放。这一机制确实与神经递质释放的促进有关,而神经递质释放是由一种有效的生物介质(垂体腺苷酸环化酶激活多肽)在SCG神经元中诱导的。我们描述了PKA和tomosyn在Ca2+依赖性神经递质释放中的作用和作用模式。
Neurotransmitter is released from nerve terminals by Ca2+-dependent exocytosis through many steps. SNARE proteins are key components at the priming and fusion steps, and the priming step is modulated by cAMP-dependent protein kinase (PKA), which causes synaptic plasticity. We show that the SNARE regulatory protein tomosyn is directly phosphorylated by PKA, which reduces its interaction with syntaxin-1 (a component of SNAREs) and enhances the formation of the SNARE complex. Electrophysiological studies using cultured superior cervical ganglion (SCG) neurons revealed that this enhanced formation of the SNARE complex by the PKA-catalyzed phosphorylation of tomosyn increased the fusion-competent readily releasable pool of synaptic vesicles and, thereby, enhanced neurotransmitter release. This mechanism was indeed involved in the facilitation of neurotransmitter release that was induced by a potent biological mediator, the pituitary adenylate cyclase-activating polypeptide, in SCG neurons. We describe the roles and modes of action of PKA and tomosyn in Ca2+-dependent neurotransmitter release.
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