Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior.
Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior.
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DOI：
10.1016/j.cub.2013.03.049
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发表时间：
2013-05-06
期刊：
影响因子：
9.2
通讯作者：
Sieburth, Derek
中科院分区：
文献类型：
--
作者：
Wang, Han;Girskis, Kelly;Janssen, Tom;Chan, Jason P.;Dasgupta, Krishnakali;Knowles, James A.;Schoofs, Liliane;Sieburth, Derek
节律行为由起搏器中的内源性生物钟驱动，起搏器必须可靠地将定时信息传输到执行节律输出的靶组织。在C.在线虫中，起搏器（肠）中的钙振荡（约每50秒发生一次）通过下游GABA能神经元触发肠肌的节律性收缩，所述GABA能神经元支配肠肌。然而，由起搏器释放的定时信号的身份和将定时信息传递到GABA能神经元的机制尚不清楚。在这里，我们表明，神经肽样蛋白（NLP-40）释放的起搏器触发一个单一的快速钙瞬变的GABA能神经元在每个排便周期。我们发现缺乏nlp-40的突变体具有正常的起搏功能，但缺乏肠肌收缩。NLP-40经历由钙传感器SNT-2/突触结合蛋白介导的钙依赖性释放。我们鉴定了GABA能神经元上的G蛋白偶联受体AEX-2作为NLP-40的受体。功能性钙成像显示，NLP-40和AEX-2/GPCR都是这些神经元节律性激活所必需的。此外，急性应用合成的NLP-40衍生肽使体内GABA能神经元去极化。我们的研究结果表明，NLP-40通过钙依赖性释放携带来自起搏器的定时信息，并通过指示其激活将其传递给GABA能神经元。因此，我们提出神经肽的节律性释放可以将时间信息从起搏器传递到下游神经元以执行节律性行为。
Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 seconds, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Here we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G protein-coupled receptor on the GABAergic neurons, as the receptor of NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors.
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影响因子：
16.2
作者：
Hu Z;Pym EC;Babu K;Vashlishan Murray AB;Kaplan JM
通讯作者：
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影响因子：
3.3
作者：
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DOI：
10.1016/j.bbrc.2005.03.071
发表时间：
2005-05-13
影响因子：
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影响因子：
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作者：
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通讯作者：
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