Entry Name Circadian entrainment
Description Circadian entrainment is a fundamental property by which the period of the internal biological clock is entrained by recurring exogenous signals, such that the organism's endocrine and behavioral rhythms are synchronized to environmental cues. In mammals, a master clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and may synchronize circadian oscillators in peripheral tissues. Light signal is the dominant synchronizer for master SCN clock. Downstream from the retina, glutamate and PACAP are released and trigger the activation of signal transduction cascades, including CamKII and nNOS activity, cAMP- and cGMP-dependent protein kinases, and mitogen-activated protein kinase (MAPK). Of non-photic entrainment, important phase shifting capabilities have been found for melatonin, which inhibits light-induced phase shifts through inhibition of adenylate cyclase (AC). Multiple entrainment pathways converge into CREB regulation. In turn, phosphorylated CREB activates clock gene expression.
Class Organismal Systems; Environmental adaptationBRITE hierarchy
Pathway map Other DBs Orthology K02633 PER2; period circadian protein 2
K04285 MTNR1A; melatonin receptor type 1A
K04286 MTNR1B; melatonin receptor type 1B
K04347 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04379 FOS; proto-oncogene protein c-fos
K04445 RPS6KA5, MSK1; ribosomal protein S6 kinase alpha-5 [EC:2.7.11.1 ]
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04534 GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha
K04536 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K04538 GNB4; guanine nucleotide-binding protein subunit beta-4
K04539 GNB5; guanine nucleotide-binding protein subunit beta-5
K04540 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04547 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04587 ADCYAP1R1, PACAPRI; pituitary adenylate cyclase-activating polypeptide type I receptor
K04630 GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04850 CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04851 CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K04854 CACNA1G, CAV3.1; voltage-dependent calcium channel T type alpha-1G
K04855 CACNA1H, CAV3.2; voltage-dependent calcium channel T type alpha-1H
K04856 CACNA1I, CAV3.3; voltage-dependent calcium channel T type alpha-1I
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3
K04961 RYR1; ryanodine receptor 1
K04962 RYR2; ryanodine receptor 2
K04963 RYR3; ryanodine receptor 3
K04997 KCNJ3, KIR3.1; potassium inwardly-rectifying channel subfamily J member 3
K04999 KCNJ5, KIR3.4; potassium inwardly-rectifying channel subfamily J member 5
K05000 KCNJ6, KIR3.2; potassium inwardly-rectifying channel subfamily J member 6
K05002 KCNJ9, KIR3.3; potassium inwardly-rectifying channel subfamily J member 9
K05197 GRIA1; glutamate receptor 1
K05198 GRIA2; glutamate receptor 2
K05199 GRIA3; glutamate receptor 3
K05200 GRIA4; glutamate receptor 4
K05208 GRIN1; glutamate receptor ionotropic, NMDA 1
K05209 GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210 GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05211 GRIN2C; glutamate receptor ionotropic, NMDA 2C
K05212 GRIN2D; glutamate receptor ionotropic, NMDA 2D
K05262 ADCYAP; pituitary adenylate cyclase-activating polypeptide
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K07825 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K07826 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K07843 RASD1; RAS, dexamethasone-induced Ras-related protein 1
K12318 GUCY1A; guanylate cyclase soluble subunit alpha [EC:4.6.1.2 ]
K12319 GUCY1B; guanylate cyclase soluble subunit beta [EC:4.6.1.2 ]
K16513 NOS1AP, CAPON; carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein
K21944 PER1; period circadian protein 1
K21945 PER3; period circadian protein 3
Compound Reference Authors Brown TM, Piggins HD
Title Electrophysiology of the suprachiasmatic circadian clock.
Journal Reference Authors Dickson L, Finlayson K
Title VPAC and PAC receptors: From ligands to function.
Journal Reference Authors Golombek DA, Rosenstein RE
Title Physiology of circadian entrainment.
Journal Reference Authors Dubocovich ML, Markowska M
Title Functional MT1 and MT2 melatonin receptors in mammals.
Journal Reference Authors Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J
Title International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors.
Journal Reference Authors Hardeland R
Title Melatonin: signaling mechanisms of a pleiotropic agent.
Journal Reference Authors Golombek DA, Ferreyra GA, Agostino PV, Murad AD, Rubio MF, Pizzio GA, Katz ME, Marpegan L, Bekinschtein TA
Title From light to genes: moving the hands of the circadian clock.
Journal Reference Authors Mertens I, Husson SJ, Janssen T, Lindemans M, Schoofs L
Title PACAP and PDF signaling in the regulation of mammalian and insect circadian rhythms.
Journal Reference Authors Kim DY, Choi HJ, Kim JS, Kim YS, Jeong DU, Shin HC, Kim MJ, Han HC, Hong SK, Kim YI
Title Voltage-gated calcium channels play crucial roles in the glutamate-induced phase shifts of the rat suprachiasmatic circadian clock.
Journal Reference Authors Agostino PV, Ferreyra GA, Murad AD, Watanabe Y, Golombek DA
Title Diurnal, circadian and photic regulation of calcium/calmodulin-dependent kinase II and neuronal nitric oxide synthase in the hamster suprachiasmatic nuclei.
Journal Reference Authors Ferreyra GA, Golombek DA
Title Rhythmicity of the cGMP-related signal transduction pathway in the mammalian circadian system.
Journal Reference Authors Butcher GQ, Lee B, Cheng HY, Obrietan K
Title Light stimulates MSK1 activation in the suprachiasmatic nucleus via a PACAP-ERK/MAP kinase-dependent mechanism.
Journal Reference Authors Hamada T, Niki T, Ziging P, Sugiyama T, Watanabe S, Mikoshiba K, Ishida N
Title Differential expression patterns of inositol trisphosphate receptor types 1 and 3 in the rat suprachiasmatic nucleus.
Journal Reference Authors Diaz-Munoz M, Dent MA, Granados-Fuentes D, Hall AC, Hernandez-Cruz A, Harrington ME, Aguilar-Roblero R
Title Circadian modulation of the ryanodine receptor type 2 in the SCN of rodents.
Journal Reference Authors Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH
Title Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON.
Journal Reference Authors Takahashi H, Umeda N, Tsutsumi Y, Fukumura R, Ohkaze H, Sujino M, van der Horst G, Yasui A, Inouye ST, Fujimori A, Ohhata T, Araki R, Abe M
Title Mouse dexamethasone-induced RAS protein 1 gene is expressed in a circadian rhythmic manner in the suprachiasmatic nucleus.
Journal Reference Authors Cheng HY, Dziema H, Papp J, Mathur DP, Koletar M, Ralph MR, Penninger JM, Obrietan K
Title The molecular gatekeeper Dexras1 sculpts the photic responsiveness of the mammalian circadian clock.
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