Drosophila pacemaker neurons require g protein signaling and GABAergic inputs to generate twenty-four hour behavioral rhythms.

Drosophila pacemaker neurons require g protein signaling and GABAergic inputs to generate twenty-four hour behavioral rhythms.
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DOI:
10.1016/j.neuron.2010.11.017
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发表时间:
2010-12-09
期刊:
影响因子:
16.2
通讯作者:
Blau J
Blau J
中科院分区:
医学1区
文献类型:
--
作者:
Dahdal D;Reeves DC;Ruben M;Akabas MH;Blau J

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细胞间信号传导对于精确的昼夜节律非常重要。在果蝇中,小腹侧神经元(s-LNvs)是主要的起搏器神经元,并在持续黑暗中设定大多数其他时钟神经元的速度。在这里,我们发现LNvs需要两个不同的g蛋白信号通路来维持24小时的节律。减少LNvs通过g - α亚基g发出的信号,g - α亚基g通过cAMP发出信号,或者通过g - α亚基Go,我们通过磷脂酶21c发出信号,延长行为节律的周期。相比之下,组成型g或Go信号使大多数果蝇无节律性。在培养中使用解离的LNvs,我们发现Go和代谢性GABAB-R3受体是GABA抑制LNvs的必要条件,GABAB-R3在体内表达减少延长了时间。虽然没有时钟神经元产生GABA,但超兴奋的GABA能神经元会破坏行为节律和s-LNv分子钟。因此,s-LNvs需要24小时节律的gaba能输入。
Intercellular signaling is important for accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LNvs) are the dominant pacemaker neurons and set the pace of most other clock neurons in constant darkness. Here we show that two distinct G-protein signaling pathways are required in LNvs for 24hr rhythms. Reducing signaling in LNvs via the G-alpha subunit Gs, which signals via cAMP, or via the G-alpha subunit Go, which we show signals via Phospholipase 21c, lengthens the period of behavioral rhythms. In contrast, constitutive Gs or Go signaling makes most flies arrhythmic. Using dissociated LNvs in culture, we found that Go and the metabotropic GABAB-R3 receptor are required for the inhibitory effects of GABA on LNvs and that reduced GABAB-R3 expression in vivo lengthens period. Although no clock neurons produce GABA, hyper-exciting GABAergic neurons disrupts behavioral rhythms and s-LNv molecular clocks. Therefore, s-LNvs require GABAergic inputs for 24hr rhythms.
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