Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus
Abstract
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.
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When PK2 binds to PK-R2, signaling cascades important for development of the olfactory system and GnRH neuronal progenitors are initiated.
“When PK2 binds to PK-R2, signaling cascades that are important for development of the olfactory system and GnRH neuronal progenitors are initiated.”
From The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism (2009) · cites this paper as [23]
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References 49 · Cited by 715
- Authors
- Cheng, M. Y., Bullock, C. M., Li, C., Lee, A. G., Bermak, J. C., Belluzzi, J., Weaver, D. R., Leslie, F. M., & Zhou, Q.-Y.
- Affiliations
- University of California, Irvine (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Zhou, Qun-Yong
- Venue
- Nature
- Published
- 2002-05
- Volume
- 417
- Issue
- 6887
- Pages
- 405-410
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2002006123
- Cited by
- 715
- References
- 49
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 19 · 2023: 17 · 2022: 9 · 2021: 28 · 2020: 28 · 2019: 20 · 2018: 24 · 2017: 17 · 2016: 24 · 2015: 16 · 2014: 32 · 2013: 34 · 2012: 28
- FWCI
- 14.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- University of California, Irvine
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- prokineticin 2, suprachiasmatic nucleus, circadian rhythm, clock-controlled genes, PROKR2, behavioural rhythms, light entrainment, positive feedback, gene expression rhythms
- MeSH terms
- Animals, Biological Clocks, Cell Line, Circadian Rhythm, Gastrointestinal Hormones, Gene Expression Regulation, Humans, Light, Male, Mice, Inbred C57BL, Motor Activity, Mutation, Neuropeptides, Protein Binding, RNA, Messenger, Suprachiasmatic Nucleus, Transcription, Genetic, 3T3 Cells, Gene Deletion, Mice, Knockout, Mice
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