Institute of Neuro- and Behavioral Biology, Westfälische Wilhelms University, 48149 Münster, Germany.
Department of Physiology, Development, and Neuroscience, Cambridge University, Cambridge CB2 3DY, UK.
Curr Biol. 2018 Jun 4;28(11):1725-1735.e3. doi: 10.1016/j.cub.2018.04.016. Epub 2018 May 17.
The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical visual phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye.
昼夜节律的日周期变化代表着使生物钟同步的关键信号。昆虫和哺乳动物都拥有专门的“生物钟”感光器，但也利用视觉系统来重置生物钟。在果蝇中，生物钟的重置是通过蓝光照感光器隐花色素（CRY）实现的，CRY 表达于脑时钟神经元的亚群中。此外，表达视紫红质的感光细胞有助于光同步。CRY 依赖性降解时钟蛋白 Timeless（TIM）使光重置分子钟，尽管在包括小腹外侧神经元（s-LNv）在内的关键生物钟起搏神经元的特定亚群中，TIM 和 Period（PER）振荡可以独立于 CRY 和经典视觉视蛋白光转导而被光同步。在这里，我们表明，至少七种果蝇视蛋白中的三种可以利用涉及在经典视觉光转导中起作用的三聚体 G 蛋白相同α亚基的替代转导机制（Gq）。令人惊讶的是，在缺乏经典磷脂酶 C-β（PLC-β）的突变体中，该 PLC-β由编码无受体电位 A（norpA）基因编码，我们发现了一种使用由 Plc21C 基因编码的不同 PLC-β的新转导途径。该新途径对于行为时钟对半自然光-暗循环的重置以及在 s-LNv 时钟神经元中介导光依赖性分子同步很重要。相同的途径似乎负责 norpA 独立的复眼中的光反应。我们表明，存在于视网膜感光细胞 R8 亚群中的视蛋白 5（Rh5）和 Rh6 驱动眼睛中的长期生物钟和快速光反应。
