Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus
Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus
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DOI：
10.1038/417405a
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发表时间：
2002-05-23
期刊：
影响因子：
64.8
通讯作者：
Zhou, QY
中科院分区：
文献类型：
--
作者：
Cheng, MY;Bullock, CM;Zhou, QY
视交叉上核（SCN）控制哺乳动物生理和行为过程的昼夜节律。在这里，我们表明，prokineticin 2（PK2），一个富含半胱氨酸的分泌蛋白，作为一个输出分子从SCN的昼夜节律钟。PK2信使RNA在SCN中有节律地表达，并且PK2节律的相位响应于光夹带。分子和遗传学研究表明，PK2是一种受生物钟控制的基因。PK2受体（PKR2）在SCN输出途径的主要靶核中大量表达。当内源性PK2 mRNA水平较低时，在主观夜间通过脑室内递送重组PK2抑制大鼠的夜间自主活动，进一步支持PK2是传递行为昼夜节律的输出分子的假设。SCN内PKR2 mRNA的高表达和PK2通过PKR2的激活对其自身转录的正反馈表明PK2也可以在SCN内局部起作用以同步输出。
The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. Here we show that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock (clock-controlled). Receptor for PK2 (PKR2) is abundantly expressed in major target nuclei of the SCN output pathway. Inhibition of nocturnal locomotor activity in rats by intracerebroventricular delivery of recombinant PK2 during subjective night, when the endogenous PK2 mRNA level is low, further supports the hypothesis that PK2 is an output molecule that transmits behavioural circadian rhythm. The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output.