Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus.
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.
Cheng
Michelle Y
MY
Department of Pharmacology, University of California, Irvine, California 92697, USA.
Bullock
Clayton M
CM
Li
Chuanyu
C
Lee
Alex G
AG
Bermak
Jason C
JC
Belluzzi
James
J
Weaver
David R
DR
Leslie
Frances M
FM
Zhou
Qun-Yong
QY
D016475:3T3 Cells; D000818:Animals; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009154:Mutation; D009479:Neuropeptides; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014158:Transcription, Genetic
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; C486586:Prok2 protein, mouse; D012333:RNA, Messenger