Suprachiasmatic nucleus clock time in the mammalian circadian system.

The integration of time from gene to system levels is an exciting feature of circadian biology. In mammals, clock cells in the suprachiasmatic nucleus (SCN) generate time by an autoregulatory transcription-(post)translational feedback loop. Clock activity in the SCN neurons is expressed as activity-dependent electric signals, which are coupled to those of other SCN neurons. The SCN spreads the time signals in a form of synchronized nerve impulses to central parasympathetic nuclei (e.g., dorsal motor nucleus of the vagus) and central sympathetic nuclei (e.g., intermediolateral cell column of the spinal cord). The vagal nerve innervates gastrointestinal and respiratory organs. Sympathetic signals to the adrenal gland are converted to hormonal (glucocorticoid) signals. Glucocorticoids released into the bloodstream bind to glucocorticoid receptors of peripheral organs, activate the mammalian Per1 gene in systemic cells, and reset the time of body clocks. Thus, the SCN-evoked time generated by specific genes localized to the SCN is converted to neuronal and hormonal signals and synchronizes the clocks in the whole body.

[1]  Steven A. Brown,et al.  Resetting of circadian time in peripheral tissues by glucocorticoid signaling. , 2000, Science.

[2]  S. Yamaguchi,et al.  Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. , 2001, Genes & development.

[3]  David C. Klein,et al.  Suprachiasmatic nucleus : the mind's clock , 1991 .

[4]  G. Tsujimoto,et al.  Light activates the adrenal gland: timing of gene expression and glucocorticoid release. , 2005, Cell metabolism.

[5]  Erin L. McDearmon,et al.  Dissecting the Functions of the Mammalian Clock Protein BMAL1 by Tissue-Specific Rescue in Mice , 2006, Science.

[6]  S. Yamaguchi,et al.  Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo , 2003, Science.

[7]  Paolo Sassone-Corsi,et al.  Circadian Regulator CLOCK Is a Histone Acetyltransferase , 2006, Cell.

[8]  Masaki Tanaka,et al.  REVIEW ■ : The Suprachiasmatic Nucleus: A Circadian Oscillator , 1997 .

[9]  A. Kalsbeek,et al.  Hypothalamic integration of central and peripheral clocks , 2001, Nature Reviews Neuroscience.

[10]  Yoshinobu Yamamoto,et al.  Role of Cyclic mPer2 Expression in the Mammalian Cellular Clock , 2005, Molecular and Cellular Biology.

[11]  R. Jordan,et al.  Circadian variation of cell proliferation and cell cycle protein expression in man: clinical implications. , 2000, Progress in cell cycle research.

[12]  B. H. Miller,et al.  Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock , 2002, Cell.

[13]  Joseph S. Takahashi,et al.  Circadian Mutant Overtime Reveals F-box Protein FBXL3 Regulation of Cryptochrome and Period Gene Expression , 2007, Cell.

[14]  K. Yagita,et al.  Does mPER2 protein oscillate without its coding mRNA cycling?: post‐transcriptional regulation by cell clock , 2006, Genes to cells : devoted to molecular & cellular mechanisms.

[15]  S. Shibata,et al.  Gene expression: View of a mouse clock gene ticking , 2001, Nature.

[16]  F. Tamanini,et al.  Molecular Mechanisms of the Biological Clock in Cultured Fibroblasts , 2001, Science.

[17]  B. Lee,et al.  BMAL1 Shuttling Controls Transactivation and Degradation of the CLOCK/BMAL1 Heterodimer , 2006, Molecular and Cellular Biology.

[18]  D. Virshup,et al.  Post-translational modifications regulate the ticking of the circadian clock , 2007, Nature Reviews Molecular Cell Biology.

[19]  S. Yamaguchi,et al.  Suprachiasmatic Nucleus Grafts Restore Circadian Behavioral Rhythms of Genetically Arrhythmic Mice , 2003, Current Biology.

[20]  U. Schibler,et al.  A Serum Shock Induces Circadian Gene Expression in Mammalian Tissue Culture Cells , 1998, Cell.

[21]  F. Davis,et al.  Transplanted suprachiasmatic nucleus determines circadian period. , 1990, Science.

[22]  Steven M. Reppert,et al.  Rhythmic histone acetylation underlies transcription in the mammalian circadian clock , 2003, Nature.

[23]  H. Okamura,et al.  Vagal Regulation of Respiratory Clocks in Mice , 2007, The Journal of Neuroscience.

[24]  F. Tamanini,et al.  Nucleocytoplasmic shuttling and mCRY‐dependent inhibition of ubiquitylation of the mPER2 clock protein , 2002, The EMBO journal.

[25]  P. Sassone-Corsi,et al.  Phenotypic Rescue of a Peripheral Clock Genetic Defect via SCN Hierarchical Dominance , 2002, Cell.

[26]  Jeffrey C. Hall,et al.  Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels , 1990, Nature.

[27]  Michele Pagano,et al.  SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins , 2007, Science.

[28]  M. Pagano,et al.  The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period , 2007, Science.

[29]  R. Moore,et al.  A retinohypothalamic projection in the rat , 1972, The Journal of comparative neurology.

[30]  Kai-Florian Storch,et al.  Extensive and divergent circadian gene expression in liver and heart , 2002, Nature.

[31]  S. Reppert,et al.  Coordination of circadian timing in mammals , 2002, Nature.

[32]  R. Moore,et al.  Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. , 1972, Brain research.

[33]  K. Yagita,et al.  Expression of ubiquitin-related enzymes in the suprachiasmatic nucleus with special reference to ubiquitin carboxy-terminal hydrolase UchL1. , 2005, Biomedical research.

[34]  松尾 拓哉 Control mechanism of the circadian clock for timing of cell division in vivo , 2004 .

[35]  S. Shibata,et al.  Adrenergic regulation of clock gene expression in mouse liver , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. T. Inouye,et al.  Persistence of circadian rhythmicity in a mammalian hypothalamic "island" containing the suprachiasmatic nucleus. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Antoch,et al.  BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. , 2003, Genes & development.

[38]  Paolo Sassone-Corsi,et al.  A Web of Circadian Pacemakers , 2002, Cell.

[39]  H. Okamura Clock Genes in Cell Clocks: Roles, Actions, and Mysteries , 2004, Journal of biological rhythms.

[40]  Lily Yan,et al.  Light-Induced Resetting of a Mammalian Circadian Clock Is Associated with Rapid Induction of the mPer1 Transcript , 1997, Cell.

[41]  H. Okamura,et al.  Chronic treatment with prednisolone represses the circadian oscillation of clock gene expression in mouse peripheral tissues. , 2006, Molecular endocrinology.

[42]  S. Yamaguchi,et al.  Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus , 2003, Science.