JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS
JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS
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DOI：
10.1126/science.1124951
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发表时间：
2006-06-23
期刊：
影响因子：
56.9
通讯作者：
Sehgal, Amita
中科院分区：
文献类型：
--
作者：
Koh, Kyunghee;Zheng, Xiangzhong;Sehgal, Amita
从细菌到人类，各种生物的生物钟都与昼夜循环同步。果蝇生物钟的光携带是由生物钟蛋白TIMELESS （TIM）的蛋白酶体降解介导的。我们已经确定了时差（一种编码富含亮氨酸重复序列的F-box蛋白的基因）的突变，这种突变会导致生物钟对光的敏感度降低。突变果蝇在恒定光下表现出有节奏的行为，对光脉冲的响应减少了相移，并且减少了光依赖性的TIM降解。在培养的S2R+细胞中，JET和昼夜节律光感受器隐色素（CRY）的表达赋予TIM光依赖性降解，从而在细胞培养系统中重建昼夜节律钟对光的急性反应。我们的研究结果表明，JET通过将光信号从CRY传输到TIM来重置时钟是必不可少的。
Organisms ranging from bacteria to humans synchronize their internal clocks to daily cycles of light and dark. Photic entrainment of the Drosophila clock is mediated by proteasomal degradation of the clock protein TIMELESS (TIM). We have identified mutations in jetlag-a gene coding for an F-box protein with leucine-rich repeats-that result in reduced light sensitivity of the circadian clock. Mutant flies show rhythmic behavior in constant light, reduced phase shifts in response to light pulses, and reduced light-dependent degradation of TIM. Expression of JET along with the circadian photoreceptor cryptochrome (CRY) in cultured S2R+ cells confers light-dependent degradation onto TIM, thereby reconstituting the acute response of the circadian clock to light in a cell culture system. Our results suggest that JET is essential for resetting the clock by transmitting light signals from CRY to TIM.