Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus
Department of Neurobiology; Weaver Lab
3T3 Cells; Animals; Biological Clocks; Cell Line; Circadian Rhythm; Gastrointestinal Hormones; Gene Deletion; Gene Expression Regulation; Humans; Light; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Mutation; *Neuropeptides; Protein Binding; RNA, Messenger; Suprachiasmatic Nucleus; Transcription, Genetic
Neuroscience and Neurobiology
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.
DOI of Published Version
Nature. 2002 May 23;417(6887):405-10. Link to article on publisher's site
Cheng, Michelle Y.; Bullock, Clayton M.; Li, Chuanyu; Lee, Alex G.; Bermak, Jason C.; Belluzzi, James; Weaver, David R.; Leslie, Frances M.; and Zhou, Qun-Yong, "Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus" (2002). Neurobiology Publications and Presentations. 93.