Speed control: Cogs and gears that drive the circadian clock

Trends in Neurosciences

Volumn 35, Issue 9, 2012, Pages 574-585

  Zheng, Xiangzhong ^a   Sehgal, Amita ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Circadian period; Kinase; Nuclear localization; Phosphatase; Phosphorylation; Stability

Indexed keywords

CASEIN KINASE I; CASEIN KINASE IEPSILON; CASEIN KINASE II; CRYPTOCHROME 1; CRYPTOCHROME 2; DOUBLETIME PROTEIN; GLYCOGEN SYNTHASE KINASE 3; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LARK PROTEIN; PER1 PROTEIN; PER2 PROTEIN; PROTEIN; PROTEIN TIMELESS; TARGET OF RAPAMYCIN KINASE; TAU PROTEIN; TRANSCRIPTION FACTOR CLOCK; UNCLASSIFIED DRUG;

BIOLOGICAL RHYTHM; CELL GROWTH; CELL SURVIVAL; CIRCADIAN RHYTHM; CIRCADIAN RHYTHM SLEEP DISORDER; CYTOPLASM; DROSOPHILA; ENZYME ACTIVITY; FAMILIAL ADVANCED SLEEP PHASE SYNDROME; GAIN OF FUNCTION MUTATION; GENE EXPRESSION; HUMAN; INTRACELLULAR SIGNALING; NEGATIVE FEEDBACK; NONHUMAN; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DEPHOSPHORYLATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; REVIEW; RNA TRANSLATION; SIGNAL TRANSDUCTION;

ANIMALS; BIOLOGICAL CLOCKS; CIRCADIAN CLOCKS; CIRCADIAN RHYTHM SIGNALING PEPTIDES AND PROTEINS; FEEDBACK, PHYSIOLOGICAL; HUMANS; SUPRACHIASMATIC NUCLEUS; TRANSCRIPTIONAL ACTIVATION;

EID: 84865571932     PISSN: 01662236     EISSN: 1878108X     Source Type: Journal    
DOI: 10.1016/j.tins.2012.05.007     Document Type: Review

References (159)

1. Foster R.G., Roenneberg T. Human responses to the geophysical daily, annual and lunar cycles. Curr. Biol. 2008, 18:R784-R794.
2. Bechtold D.A., et al. Circadian dysfunction in disease. Trends Pharmacol. Sci. 2010, 31:191-198.
3. Benca R., et al. Biological rhythms, higher brain function, and behavior: gaps, opportunities, and challenges. Brain Res. Rev. 2009, 62:57-70.
4. Mackey S.R., et al. The itty-bitty time machine: genetics of the cyanobacterial circadian clock. Adv. Genet. 2011, 74:13-53.
5. Allada R., et al. A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell 1998, 93:791-804.
6. Rutila J.E., et al. CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless. Cell 1998, 93:805-814.
7. Bae K., et al. dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex. J. Neurosci. 2000, 20:1746-1753.
8. Houl J.H., et al. Drosophila CLOCK is constitutively expressed in circadian oscillator and non-oscillator cells. J. Biol. Rhythms 2006, 21:93-103.
9. Konopka R., Benzer S. Clock mutants of Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 1971, 68:2112-2116.
10. Bargiello T., et al. Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 1984, 312:752-754.
11. Reddy P., et al. Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms. Cell 1984, 38:701-710.
12. Zehring W.A., et al. P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 1984, 39:369-376.
13. Myers M., et al. Positional cloning and sequence analysis of the Drosophila clock gene, timeless. Science 1995, 270:805-808.
14. Sehgal A., et al. Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science 1994, 263:1603-1606.
15. Sehgal A., et al. Rhythmic expression of timeless: a basis for promoting circadian cycles in period gene autoregulation. Science 1995, 270:808-810.
16. Hao H., et al. A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila melanogaster. Mol. Cell. Biol. 1997, 17:3687-3693.
17. Darlington T.K., et al. Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science 1998, 280:1599-1603.
18. Lee C., et al. PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription. Mol. Cell. Biol. 1999, 19:5316-5325.
19. Menet J.S., et al. Dynamic PER repression mechanisms in the Drosophila circadian clock: from on-DNA to off-DNA. Genes Dev. 2010, 24:358-367.
20. Cyran S.A., et al. vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell 2003, 112:329-341.
21. Glossop N.R.J., et al. VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator. Neuron 2003, 37:249-261.
22. Yu W., et al. PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription. Genes Dev. 2006, 20:723-733.
23. Kim E.Y., et al. Drosophila CLOCK protein is under posttranscriptional control and influences light-induced activity. Neuron 2002, 34:69-81.
24. Renn S.C.P., et al. A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila. Cell 1999, 99:791-802.
25. Zheng X., et al. An isoform-specific mutant reveals a role of PDP1e{open} in the circadian oscillator. J. Neurosci. 2009, 29:10920-10927.
26. Akashi M., Takumi T. The orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1. Nat. Struct. Mol. Biol. 2005, 12:441-448.
27. Nakajima Y., et al. Bidirectional role of orphan nuclear receptor RORα in clock gene transcriptions demonstrated by a novel reporter assay system. FEBS Lett. 2004, 565:122-126.
28. Sato T.K., et al. A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 2004, 43:527-537.
29. Preitner N., et al. The orphan nuclear receptor REV-ERBα controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 2002, 110:251-260.
30. Crumbley C., Burris T.P. Direct regulation of CLOCK expression by REV-ERB. PLoS ONE 2011, 6:e17290.
31. Liu A.C., et al. Redundant function of REV-ERB α and β and non-essential role for Bmal1 cycling in transcriptional regulation of intracellular circadian rhythms. PLoS Genet. 2008, 4:e1000023.
32. Cho H., et al. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 2012, 485:123-127.
33. Herzog E.D., et al. Clock controls circadian period in isolated suprachiasmatic nucleus neurons. Nat. Neurosci. 1998, 1:708-713.
34. Nakamura W., et al. Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons. Nat. Neurosci. 2002, 5:399-400.
35. Vitaterna M.H., et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 1994, 264:719-725.
36. Blau J., Young M.W. Cycling vrille expression is required for a functional Drosophila clock. Cell 1999, 99:661-671.
37. Smith R.F., Konopka R.J. Effects of dosage alterations at the per locus on the period of the circadian clock of Drosophila. Mol. Gen. Genet. 1982, 185:30-36.
38. Baylies M.K., et al. Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock. Nature 1987, 326:390-392.
39. Hao H., et al. The 69bp circadian regulatory sequence (CRS) mediates per-like developmental, spatial, and circadian expression and behavioral rescue in Drosophila. J. Neurosci. 1999, 19:987-994.
40. Ashmore L.J., et al. Novel insights into the regulation of the Timeless protein. J. Neurosci. 2003, 23:7810-7819.
41. Yang Z., Sehgal A. Role of molecular oscillations in generating behavioral rhythms in Drosophila. Neuron 2001, 29:453-467.
42. Zhao J., et al. Drosophila Clock can generate ectopic circadian clocks. Cell 2003, 113:755-766.
43. Kadener S., et al. Circadian transcription contributes to core period determination in Drosophila. PLoS Biol. 2008, 6:e119.
44. Antoch M.P., et al. Functional identification of the mouse circadian clock gene by transgenic BAC rescue. Cell 1997, 89:655-667.
45. Numano R., et al. Constitutive expression of the Period1 gene impairs behavioral and molecular circadian rhythms. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:3716-3721.
46. Glossop N., et al. Interlocked feedback loops within the Drosophila circadian oscillator. Science 1999, 286:766-768.
47. Lim C., et al. clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Curr. Biol. 2007, 17:1082-1089.
48. Kadener S., et al. Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component. Genes Dev. 2007, 21:1675-1686.
49. Matsumoto A., et al. A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes Dev. 2007, 21:1687-1700.
50. Nakashima A., et al. DEC1 modulates the circadian phase of clock gene expression. Mol. Cell. Biol. 2008, 28:4080-4092.
51. Bode B., et al. Genetic interaction of Per1 and Dec1/2 in the regulation of circadian locomotor activity. J. Biol. Rhythms 2011, 26:530-540.
52. Lim C., et al. The novel gene twenty-four defines a critical translational step in the Drosophila clock. Nature 2011, 470:399-403.
53. Kojima S., et al. LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:1859-1864.
54. Huang Y., et al. Altered LARK expression perturbs development and physiology of the Drosophila PDF clock neurons. Mol. Cell. Neurosci. 2009, 41:196-205.
55. Newby L.M., Jackson F.R. A new biological rhythm mutant of Drosophila melanogaster that identifies a gene with an essential embryonic function. Genetics 1993, 135:1077-1090.
56. Kloss B., et al. The Drosophila Clock gene double-time encodes a protein closely related to human casein kinase I e{open}. Cell 1998, 94:97-107.
57. Price J.L., et al. double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 1998, 94:83-95.
58. Suri V., et al. TIMELESS-dependent positive and negative autoregulation in the Drosophila circadian clock. EMBO J. 1999, 18:675-686.
59. Price J., et al. Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless. EMBO J. 1995, 14:4044-4049.
60. Rothenfluh A., et al. Short-period mutations of per affect a double-time-dependent step in the Drosophila circadian clock. Curr. Biol. 2000, 10:1399-1402.
61. Muskus M.J., et al. Drosophila DBT lacking protein kinase activity produces long-period and arrhythmic circadian behavioral and molecular rhythms. Mol. Cell. Biol. 2007, 27:8049-8064.
62. Ko H.W., et al. Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime. Nature 2002, 420:673-678.
63. Preuss F., et al. Drosophila doubletime mutations which either shorten or lengthen the period of circadian rhythms decrease the protein kinase activity of casein kinase I. Mol. Cell. Biol. 2004, 24:886-898.
64. Syed S., et al. Kinetics of doubletime kinase-dependent degradation of the Drosophila Period protein. J. Biol. Chem. 2011, 286:27654-27662.
65. Suri V., et al. Two novel doubletime mutants alter circadian properties and eliminate the delay between RNA and protein in Drosophila. J. Neurosci. 2000, 20:7547-7555.
66. Kivimäe S., et al. Activating PER repressor through a DBT-directed phosphorylation switch. PLoS Biol. 2008, 6:e183.
67. S mutation delays the nuclear accumulation of period protein and affects the feedback regulation of period mRNA. J. Neurosci. 2001, 21:7117-7126.
68. Nawathean P., Rosbash M. The Doubletime and CKII kinases collaborate to potentiate Drosophila PER transcriptional repressor activity. Mol. Cell 2004, 13:213-223.
69. S flies: evidence for light-mediated delay of the negative feedback loop in Drosophila. EMBO J. 1996, 15:6877-6886.
70. Chiu J.C., et al. NEMO/NLK phosphorylates PERIOD to initiate a time-delay phosphorylation circuit that sets circadian clock speed. Cell 2011, 145:357-370.
71. Grima B., et al. The F-box protein Slimb controls the levels of clock proteins Period and Timeless. Nature 2002, 420:178-182.
72. Yu W., et al. NEMO kinase contributes to core period determination by slowing the pace of the Drosophila circadian oscillator. Curr. Biol. 2011, 21:756-761.
73. Chiu J.C., et al. The phospho-occupancy of an atypical SLIMB-binding site on PERIOD that is phosphorylated by DOUBLETIME controls the pace of the clock. Genes Dev. 2008, 22:1758-1772.
74. Akashi M., et al. Control of intracellular dynamics of mammalian Period proteins by casein Kinase I e{open} (CKIe{open}) and CKIδ in cultured cells. Mol. Cell. Biol. 2002, 22:1693-1703.
75. Meng Q.-J., et al. Setting clock speed in mammals: The CK1e{open} tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins. Neuron 2008, 58:78-88.
76. Eide E.J., et al. Control of mammalian circadian rhythm by CKIe{open}-regulated proteasome-mediated PER2 degradation. Mol. Cell. Biol. 2005, 25:2795-2807.
77. Etchegaray J.-P., et al. Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol. Cell. Biol. 2009, 29:3853-3866.
78. Isojima Y., et al. CKIe{open}/δ-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:15744-15749.
79. Lee H., et al. Essential roles of CKIδ and CKIe{open} in the mammalian circadian clock. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:21359-21364.
80. Hirota T., et al. High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase. PLoS Biol. 2010, 8:e1000559.
81. Meng Q.-J., et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:15240-15245.
82. Walton K.M., et al. Selective inhibition of casein kinase 1e{open} minimally alters circadian clock period. J. Pharmacol. Exp. Ther. 2009, 330:430-439.
83. Xu Y., et al. Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome. Nature 2005, 434:640-644.
84. Ralph M.R., Menaker M. A mutation of the circadian system in golden hamsters. Science 1988, 241:1225-1227.
85. Lowrey P.L., et al. Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. Science 2000, 288:483-491.
86. Gallego M., et al. An opposite role for tau in circadian rhythms revealed by mathematical modeling. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:10618-10623.
87. Dey J., et al. The tau mutation in the Syrian hamster differentially reprograms the circadian clock in the SCN and peripheral tissues. J. Biol. Rhythms 2005, 20:99-110.
88. Jones C.R., et al. Familial advanced sleep-phase syndrome: a short-period circadian rhythm variant in humans. Nat. Med. 1999, 5:1062-1065.
89. Fan J.-Y., et al. Drosophila and vertebrate casein kinase Iδ exhibits evolutionary conservation of circadian function. Genetics 2009, 181:139-152.
90. Sekine T., et al. Casein kinase Ie{open} does not rescue double-time function in Drosophila despite evolutionarily conserved roles in the circadian clock. J. Biol. Rhythms 2008, 23:3-15.
91. Toh K.L., et al. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 2001, 291:1040-1043.
92. Shanware N.P., et al. Casein kinase 1-dependent phosphorylation of familial advanced sleep phase syndrome-associated residues controls PERIOD 2 stability. J. Biol. Chem. 2011, 286:12766-12774.
93. Xu Y., et al. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell 2007, 128:59-70.
94. Vanselow K., et al. Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS). Genes Dev. 2006, 20:2660-2672.
95. Kloss B., et al. Phosphorylation of PERIOD is influenced by cycling physical associations of DOUBLE-TIME, PERIOD, and TIMELESS in the Drosophila Clock. Neuron 2001, 30:699-706.
96. Sathyanarayanan S., et al. Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A. Cell 2004, 116:603-615.
97. Fang Y., et al. Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1). Genes Dev. 2007, 21:1506-1518.
98. Lee H.-M., et al. The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:16451-16456.
99. Gallego M., et al. Protein phosphatase 1 regulates the stability of the circadian protein PER2. Biochem. J. 2006, 399:169-175.
100. Lee C., et al. Posttranslational mechanisms regulate the mammalian circadian clock. Cell 2001, 107:855-867.
101. Diernfellner A.C.R., Schafmeier T. Phosphorylations: making the Neurospora crassa circadian clock tick. FEBS Lett. 2011, 585:1461-1466.
102. Afh mutations on mouse circadian behavior and molecular pacemaking. J. Neurosci. 2011, 31:1539-1544.
103. Godinho S.I.H., et al. The After-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science 2007, 316:897-900.
104. Busino L., et al. SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of Cryptochrome proteins. Science 2007, 316:900-904.
105. Siepka S.M., et al. Circadian mutant overtime reveals F-box protein FBXL3 regulation of Cryptochrome and Period gene expression. Cell 2007, 129:1011-1023.
106. Saez L., Young M.W. Regulation of nuclear entry of the Drosophila clock proteins Period and Timeless. Neuron 1996, 17:911-920.
107. Vosshall L., et al. Block in nuclear localization of period protein by a second clock mutation, timeless. Science 1994, 263:1606-1609.
108. Meyer P., et al. PER-TIM interactions in living Drosophila cells: an interval timer for the circadian clock. Science 2006, 311:226-229.
109. Shafer O.T., et al. Sequential nuclear accumulation of the clock proteins Period and Timeless in the pacemaker neurons of Drosophila melanogaster. J. Neurosci. 2002, 22:5946-5954.
110. Saez L., et al. A PER/TIM/DBT interval timer for Drosophila's circadian clock. Cold Spring Harb. Symp. Quant. Biol. 2007, 72:69-74.
111. Saez L., et al. A key temporal delay in the circadian cycle of Drosophila is mediated by a nuclear localization signal in the Timeless protein. Genetics 2011, 188:591-600.
112. Rothenfluh A., et al. Isolation and analysis of six timeless alleles that cause short- or long-period circadian rhythms in Drosophila. Genetics 2000, 156:665-675.
113. Curtin K.D., et al. Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock. Neuron 1995, 14:365-372.
114. Hara T., et al. Post-translational regulation and nuclear entry of TIMELESS and PERIOD are affected in new timeless mutant. J. Neurosci. 2011, 31:9982-9990.
115. Rothenfluh A., et al. A TIMELESS-independent function for PERIOD proteins in the Drosophila clock. Neuron 2000, 26:505-514.
116. Zerr D., et al. Circadian fluctuations of period protein immunoreactivity in the CNS and the visual system of Drosophila. J. Neurosci. 1990, 10:2749-2762.
117. Cyran S.A., et al. The Double-Time protein kinase regulates the subcellular localization of the Drosophila clock protein Period. J. Neurosci. 2005, 25:5430-5437.
118. Kim E.Y., et al. A role for O-GlcNAcylation in setting circadian clock speed. Genes Dev. 2012, 26:490-502.
119. Vielhaber E., et al. Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase Ie{open}. Mol. Cell. Biol. 2000, 20:4888-4899.
120. Lin J.-M., et al. A role for casein kinase 2α in the Drosophila circadian clock. Nature 2002, 420:816-820.
121. Akten B., et al. A role for CK2 in the Drosophila circadian oscillator. Nat. Neurosci. 2003, 6:251-257.
122. Maier B., et al. A large-scale functional RNAi screen reveals a role for CK2 in the mammalian circadian clock. Genes Dev. 2009, 23:708-718.
123. Tsuchiya Y., et al. Involvement of the protein kinase CK2 in the regulation of mammalian circadian rhythms. Sci. Signal. 2009, 2:ra26.
124. Myers M.P., et al. Light-induced degradation of TIMELESS and entrainment of the Drosophila circadian clock. Science 1996, 271:1736-1740.
125. Zeng H., et al. A light-entrainment mechanism for the Drosophila circadian clock. Nature 1996, 380:129-135.
126. Martinek S., et al. A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock. Cell 2001, 105:769-779.
127. Ko H.W., et al. A hierarchical phosphorylation cascade that regulates the timing of PERIOD nuclear entry reveals novel roles for proline-directed kinases and GSK-3β/SGG in circadian clocks. J. Neurosci. 2010, 30:12664-12675.
128. Abe M., et al. Lithium lengthens the circadian period of individual suprachiasmatic nucleus neurons. Neuroreport 2000, 11:3261-3264.
129. Iitaka C., et al. A role for glycogen synthase kinase-3β in the mammalian circadian clock. J. Biol. Chem. 2005, 280:29397-29402.
130. Kaladchibachi S., et al. Glycogen synthase kinase 3, circadian rhythms, and bipolar disorder: a molecular link in the therapeutic action of lithium. J. Circadian Rhythms 2007, 5:3.
131. Yin L., et al. Nuclear receptor Rev-erb alpha is a critical lithium-sensitive component of the circadian clock. Science 2006, 311:1002-1005.
132. Spengler M.L., et al. A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and degradation. Cell Cycle 2009, 8:4138-4146.
133. Hirota T., et al. A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3β. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:20746-20751.
134. Zhang E.E., et al. A genome-wide RNAi screen for modifiers of the circadian clock in human cells. Cell 2009, 139:199-210.
135. Lear B.C., et al. A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior. Neuron 2005, 48:221-227.
136. Mertens I., et al. PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors. Neuron 2005, 48:213-219.
137. Hyun S., et al. Drosophila GPCR Han is a receptor for the circadian clock neuropeptide PDF. Neuron 2005, 48:267-278.
138. Shafer O.T., et al. Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging. Neuron 2008, 58:223-237.
139. Yoshii T., et al. The neuropeptide pigment-dispersing factor adjusts period and phase of Drosophila's clock. J. Neurosci. 2009, 29:2597-2610.
140. Dahdal D., et al. Drosophila pacemaker neurons require G protein signaling and GABAergic inputs to generate twenty-four hour behavioral rhythms. Neuron 2010, 68:964-977.
141. Levine J.D., et al. Altered circadian pacemaker functions and cyclic AMP rhythms in the Drosophila learning mutant dunce. Neuron 1994, 13:967-974.
142. Wu M.N., et al. The effects of caffeine on sleep in Drosophila require PKA activity, but not the adenosine receptor. J. Neurosci. 2009, 29:11029-11037.
143. Oike H., et al. Caffeine lengthens circadian rhythms in mice. Biochem. Biophys. Res. Commun. 2011, 410:654-658.
144. Lamia K.A., et al. AMPK regulates the circadian clock by Cryptochrome phosphorylation and degradation. Science 2009, 326:437-440.
145. Lowrey P.L., Takahashi J.S. Genetics of circadian rhythms in mammalian model organisms. Adv. Genet. 2011, 74:175-230.
146. Um J.H., et al. Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Ie{open} (CKIe{open})-dependent degradation of clock protein mPer2. J. Biol. Chem. 2007, 282:20794-20798.
147. Zheng X., Sehgal A. AKT and TOR signaling set the pace of the circadian pacemaker. Curr. Biol. 2010, 20:1203-1208.
148. Zhang H.H., et al. S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol. Cell 2006, 24:185-197.
149. Cross D., et al. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995, 378:785-789.
150. Ogawa S., et al. A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. Brain Res. 2007, 1168:112-123.
151. Kohsaka A., et al. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 2007, 6:414-421.
152. Akten B., et al. Ribosomal S6 kinase cooperates with casein kinase 2 to modulate the Drosophila circadian molecular oscillator. J. Neurosci. 2009, 29:466-475.
153. Roenneberg T., et al. Epidemiology of the human circadian clock. Sleep Med. Rev. 2007, 11:429-438.
154. Dunlap J.C., et al. A Circadian clock in Neurospora: how genes and proteins cooperate to produce a sustained, entrainable, and compensated biological oscillator with a period of about a day. Cold Spring Harb. Symp. Quant. Biol. 2007, 72:57-68.
155. Baker C.L., et al. The circadian clock of Neurospora crassa. FEMS Microbiol. Rev. 2012, 36:95-110.
156. Baker C.L., et al. Quantitative proteomics reveals a dynamic interactome and phase-specific phosphorylation in the Neurospora circadian clock. Mol. Cell 2009, 34:354-363.
157. Karatsoreos I.N., et al. Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:1657-1662.
158. Scheer F.A.J.L., et al. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:4453-4458.
159. Roenneberg T., et al. Social jetlag and obesity. Curr. Biol. 2012, 22:939-943.