Light Sampling via Throttled Visual Phototransduction Robustly Synchronizes the Drosophila Circadian Clock
Light Sampling via Throttled Visual Phototransduction Robustly Synchronizes the Drosophila Circadian Clock
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DOI：
10.1016/j.cub.2020.04.067
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发表时间：
2020-07-06
期刊：
影响因子：
9.2
通讯作者：
Stanewsky, Ralf
中科院分区：
文献类型：
--
作者：
Ogueta, Maite;Hardie, Roger C.;Stanewsky, Ralf
光暗的日变化是生物钟与环境同步的重要线索。外部时间和内部时间之间的匹配对于生物体的健康至关重要，而去湿化与许多身心健康问题有关。因此，生物体发展了复杂的、尚未完全理解的机制，以使其生物钟与光同步。在哺乳动物和果蝇中，视觉系统和非成像光感受器都有助于生物钟重置。在果蝇中，蓝光感光器隐花色素对时钟蛋白TIMELESS的光依赖性降解被认为是时钟同步的主要机制，尽管视觉系统也有贡献。为了更好地理解视觉系统的贡献，我们产生了一种遗传变异，表现出极慢的光转导动力学，但正常的敏感性。在这种变体中，视觉系统能够将其全部份额贡献给昼夜节律钟夹带，无论是关于行为和分子光同步。这种功能取决于一种替代的磷脂酶C-β酶，由PLC 21 C编码，可能在时钟重置中发挥专门作用。我们表明，该途径需要遍在蛋白连接酶CULLIN-3，可能介导TIMELESS在光：暗循环期间的不依赖于CRY的降解。我们的研究结果表明，PLC 21 C介导的贡献，昼夜节律时钟夹带上操作的时间尺度上显着放缓相比，快速，norpA依赖的视觉光转导。因此，我们的发现与视觉系统在长时间（h）内对光进行采样的一般想法是一致的，以便可靠地将其内部时钟与外部时间同步。
The daily changes of light and dark exemplify a prominent cue for the synchronization of circadian clocks with the environment. The match between external and internal time is crucial for the fitness of organisms, and desynchronization has been linked to numerous physical and mental health problems. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and in Drosophila, both the visual system and non-image-forming photoreceptors contribute to circadian clock resetting. In Drosophila, light-dependent degradation of the clock protein TIMELESS by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the visual system also contributes. To better understand the visual system contribution, we generated a genetic variant exhibiting extremely slow phototransduction kinetics, yet normal sensitivity. In this variant, the visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular light synchronization. This function depends on an alternative phospholipase C-beta enzyme, encoded by PLC21C, presumably playing a dedicated role in clock resetting. We show that this pathway requires the ubiquitin ligase CULLIN-3, possibly mediating CRY-independent degradation of TIMELESS during light:dark cycles. Our results suggest that the PLC21C-mediated contribution to circadian clock entrainment operates on a drastically slower timescale compared with fast, norpA-dependent visual phototransduction. Our findings are therefore consistent with the general idea that the visual system samples light over prolonged periods of time (h) in order to reliably synchronize their internal clocks with the external time.