Cellular and molecular basis of circadian timing in mammals.
In mammals, a master circadian clock resides in the suprachiasmatic nuclei of the anterior hypothalamus. The suprachiasmatic nuclei is composed of multiple, single-cell circadian oscillators, which, when synchronized, lead to coordinated circadian outputs that ultimately regulate overt rhythms. Several "clock genes" have been cloned that are involved in interacting transcriptional/translational feedback loops that comprise the molecular clockwork. The daily light-dark cycle ultimately impinges on the control of 2 clock genes that reset the core clock mechanism. Output genes are also generated by the central clock mechanism, but their protein products transduce downstream effects. Greater understanding of the cellular and molecular control of the suprachiasmatic nuclei provides opportunities for pharmacological manipulation of circadian timing.
Reppert
S M
SM
Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, and Harvard Medical School, Boston 02114, USA. reppert@helix.mgh.harvard.edu
D000818:Animals; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005246:Feedback; D005420:Flavoproteins / Q000235:genetics; D006801:Humans; D008027:Light; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled; D013493:Suprachiasmatic Nucleus / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C119828:cry protein, Drosophila