Tanoue Shintaro, Krishnan Parthasarathy, Chatterjee Abhishek, Hardin Paul E
Department of Biology, Texas A&M University, College Station, Texas 77843-3258, USA.
Curr Biol. 2008 Jun 3;18(11):787-94. doi: 10.1016/j.cub.2008.04.062. Epub 2008 May 22.
The Drosophila circadian clock controls rhythms in the amplitude of odor-induced electrophysiological responses that peak during the middle of night. These rhythms are dependent on clocks in olfactory sensory neurons (OSNs), suggesting that odorant receptors (ORs) or OR-dependent processes are under clock control. Because responses to odors are initiated by heteromeric OR complexes that form odor-gated and cyclic-nucleotide-activated cation channels, we tested whether regulators of ORs were under circadian-clock control.
The levels of G protein-coupled receptor kinase 2 (Gprk2) messenger RNA and protein cycle in a circadian-clock-dependent manner with a peak around the middle of the night in antennae. Gprk2 overexpression in OSNs from wild-type or cyc(01) flies elicits constant high-amplitude electroantennogram (EAG) responses to ethyl acetate, whereas Gprk2 mutants produce constant low-amplitude EAG responses. ORs accumulate to high levels in the dendrites of OSNs around the middle of the night, and this dendritic localization of ORs is enhanced by GPRK2 overexpression at times when ORs are primarily localized in the cell body.
These results support a model in which circadian-clock-dependent rhythms in GPRK2 abundance control the rhythmic accumulation of ORs in OSN dendrites, which in turn control rhythms in olfactory responses. The enhancement of OR function by GPRK2 contrasts with the traditional role of GPRKs in desensitizing activated receptors and suggests that GPRK2 functions through a fundamentally different mechanism to modulate OR activity.
果蝇生物钟控制着气味诱导的电生理反应幅度的节律，该反应在午夜达到峰值。这些节律依赖于嗅觉感觉神经元（OSN）中的生物钟，这表明气味受体（OR）或OR依赖的过程受生物钟控制。由于对气味的反应是由形成气味门控和环核苷酸激活阳离子通道的异源OR复合物引发的，我们测试了OR的调节因子是否受昼夜节律钟控制。
G蛋白偶联受体激酶2（Gprk2）信使核糖核酸和蛋白质水平以昼夜节律钟依赖的方式循环，触角中在午夜前后达到峰值。在野生型或cyc(01)果蝇的OSN中过表达Gprk2会引发对乙酸乙酯的持续高振幅触角电图（EAG）反应，而Gprk2突变体则产生持续低振幅的EAG反应。OR在午夜前后在OSN的树突中积累到高水平，并且在OR主要定位于细胞体的时期，GPRK2过表达会增强OR的这种树突定位。
这些结果支持了一个模型，即GPRK2丰度的昼夜节律钟依赖节律控制OR在OSN树突中的节律性积累，进而控制嗅觉反应的节律。GPRK2对OR功能的增强与GPRK在使激活的受体脱敏方面的传统作用形成对比，表明GPRK2通过一种根本不同的机制来调节OR活性。
