Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
Neuron. 2010 Dec 9;68(5):964-77. doi: 10.1016/j.neuron.2010.11.017.
Intercellular signaling is important for accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LN(v)s) 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 LN(v)s for 24 hr rhythms. Reducing signaling in LN(v)s 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 LN(v)s in culture, we found that Go and the metabotropic GABA(B)-R3 receptor are required for the inhibitory effects of GABA on LN(v)s and that reduced GABA(B)-R3 expression in vivo lengthens period. Although no clock neurons produce GABA, hyperexciting GABAergic neurons disrupts behavioral rhythms and s-LN(v) molecular clocks. Therefore, s-LN(v)s require GABAergic inputs for 24 hr rhythms.
细胞间信号传递对于精确的生物钟节律很重要。在果蝇中，小腹外侧神经元（s-LN(v)s）是主要的起搏神经元，在持续黑暗中为大多数其他生物钟神经元设定节奏。在这里，我们表明，两种不同的 G 蛋白信号通路在 LN(v)s 中对于 24 小时节律是必需的。通过 G 蛋白α亚基 Gs（通过 cAMP 信号传递）或通过 G 蛋白α亚基 Go（我们表明其通过 Phospholipase 21c 信号传递）降低 LN(v)s 中的信号传递，会延长行为节律的周期。相比之下，组成型 Gs 或 Go 信号传递使大多数果蝇失去节律。在离体培养的 LN(v)s 中，我们发现 Go 和代谢型 GABA(B)-R3 受体对于 GABA 对 LN(v)s 的抑制作用是必需的，并且体内 GABA(B)-R3 表达的减少会延长周期。尽管没有时钟神经元产生 GABA，但过度兴奋的 GABA 能神经元会破坏行为节律和 s-LN(v)分子钟。因此，s-LN(v)s 需要 GABA 能输入来维持 24 小时节律。
