The Proteomic Landscape of the Suprachiasmatic Nucleus Clock Reveals Large-Scale Coordination of Key Biological Processes

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The suprachiasmatic nucleus (SCN) serves as the master circadian pacemaker in mammals, coordinating the physiological responses of a myriad of peripheral clocks throughout the body and linking their rhythms to the environmental light-dark cycle. In this study, we interrogated the murine SCN proteome across the circadian cycle using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry. Among 3275 identified proteins in the SCN, 421 displayed a time-of-day-dependent expression profile, 48 fit a circadian expression profile with a ∼24 h period, and a surprising number of proteins were ultradianly expressed. Nine circadianly expressed proteins were accompanied by transcripts that were also 24 h rhythmic, but with a significant time lag (>8 h) between the phases of peak mRNA vs. protein expression. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated dawn and dusk, and was involved in mitochondrial oxidative phosphorylation. Additionally, predicted targets of miR-133ab were enriched in specific hierarchical clusters and were inversely correlated with miR133ab expression in the SCN. Our study underscores the significance of post-transcriptional regulation, the surprising prevalence of ultradian protein expression, and the functional implications on mitochondrial energy metabolism.

Vyšlo v časopise: The Proteomic Landscape of the Suprachiasmatic Nucleus Clock Reveals Large-Scale Coordination of Key Biological Processes. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004695
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004695

Souhrn

Zdroje

1. ReppertSM, WeaverDR (2002) Coordination of circadian timing in mammals. Nature 418: 935–941.

2. MooreRY, EichlerVB (1972) Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res 42: 201–206.

3. StephanFK, ZuckerI (1972) Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci U S A 69: 1583–1586.

4. PandaS, AntochMP, MillerBH, SuAI, SchookAB, et al. (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109: 307–320.

5. UedaHR, ChenW, AdachiA, WakamatsuH, HayashiS, et al. (2002) A transcription factor response element for gene expression during circadian night. Nature 418: 534–539.

6. GreenbaumD, ColangeloC, WilliamsK, GersteinM (2003) Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol 4: 117.

7. DeeryMJ, MaywoodES, CheshamJE, SladekM, KarpNA, et al. (2009) Proteomic analysis reveals the role of synaptic vesicle cycling in sustaining the suprachiasmatic circadian clock. Curr Biol 19: 2031–2036.

8. LimC, AlladaR (2013) Emerging roles for post-transcriptional regulation in circadian clocks. Nat Neurosci 16: 1544–1550.

9. TianR, Alvarez-SaavedraM, ChengHY, FigeysD (2011) Uncovering the proteome response of the master circadian clock to light using an AutoProteome system. Mol Cell Proteomics 10 M110 007252.

10. ChangHC, GuarenteL (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153: 1448–1460.

11. MusiekES, LimMM, YangG, BauerAQ, QiL, et al. (2013) Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. J Clin Invest 123: 5389–5400.

12. IshihamaY, SatoT, TabataT, MiyamotoN, SaganeK, et al. (2005) Quantitative mouse brain proteomics using culture-derived isotope tags as internal standards. Nat Biotechnol 23: 617–621.

13. ZhouH, WangF, WangY, NingZ, HouW, et al. (2011) Improved recovery and identification of membrane proteins from rat hepatic cells using a centrifugal proteomic reactor. Mol Cell Proteomics 10 O111 008425.

14. RoblesMS, CoxJ, MannM (2014) In-vivo quantitative proteomics reveals a key contribution of post-transcriptional mechanisms to the circadian regulation of liver metabolism. PLoS Genet 10: e1004047.

15. MauvoisinD, WangJ, JouffeC, MartinE, AtgerF, et al. (2014) Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver. Proc Natl Acad Sci U S A 111: 167–172.

16. JiaoX, ShermanBT, Huang daW, StephensR, BaselerMW, et al. (2012) DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics 28: 1805–1806.

17. HughesME, HogeneschJB, KornackerK (2010) JTK_CYCLE: an efficient nonparametric algorithm for detecting rhythmic components in genome-scale data sets. J Biol Rhythms 25: 372–380.

18. HughesME, DiTacchioL, HayesKR, VollmersC, PulivarthyS, et al. (2009) Harmonics of circadian gene transcription in mammals. PLoS Genet 5: e1000442.

19. MasriS, PatelVR, Eckel-MahanKL, PelegS, ForneI, et al. (2013) Circadian acetylome reveals regulation of mitochondrial metabolic pathways. Proc Natl Acad Sci U S A 110: 3339–3344.

20. PodobedP, PyleWG, AcklooS, AlibhaiFJ, TsimakouridzeEV, et al. (2014) The day/night proteome in the murine heart. Am J Physiol Regul Integr Comp Physiol [epub ahead of print].

21. MehtaN, ChengHY (2013) Micro-managing the circadian clock: The role of microRNAs in biological timekeeping. J Mol Biol 425: 3609–3624.

22. ChengHY, PappJW, VarlamovaO, DziemaH, RussellB, et al. (2007) microRNA modulation of circadian-clock period and entrainment. Neuron 54: 813–829.

23. HeyerMP, PaniAK, SmeyneRJ, KennyPJ, FengG (2012) Normal midbrain dopaminergic neuron development and function in miR-133b mutant mice. J Neurosci 32: 10887–10894.

24. Alvarez-SaavedraM, AntounG, YanagiyaA, Oliva-HernandezR, Cornejo-PalmaD, et al. (2011) miRNA-132 orchestrates chromatin remodeling and translational control of the circadian clock. Hum Mol Genet 20: 731–751.

25. ObrietanK, ImpeyS, StormDR (1998) Light and circadian rhythmicity regulate MAP kinase activation in the suprachiasmatic nuclei. Nat Neurosci 1: 693–700.

26. NishikawaY, ShibataS, WatanabeS (1995) Circadian changes in long-term potentiation of rat suprachiasmatic field potentials elicited by optic nerve stimulation in vitro. Brain Res 695: 158–162.

27. GintyDD, KornhauserJM, ThompsonMA, BadingH, MayoKE, et al. (1993) Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science 260: 238–241.

28. WestermarkPO, HerzelH (2013) Mechanism for 12 hr rhythm generation by the circadian clock. Cell Rep 3: 1228–1238.

29. PeekCB, AffinatiAH, RamseyKM, KuoHY, YuW, et al. (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342: 1243417.

30. Desquiret-DumasV, GueguenN, LemanG, BaronS, Nivet-AntoineV, et al. (2013) Resveratrol induces a mitochondrial complex I-dependent increase in NADH oxidation responsible for sirtuin activation in liver cells. J Biol Chem 288: 36662–36675.

31. RamseyKM, YoshinoJ, BraceCS, AbrassartD, KobayashiY, et al. (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324: 651–654.

32. DallmannR, ViolaAU, TarokhL, CajochenC, BrownSA (2012) The human circadian metabolome. Proc Natl Acad Sci USA 109: 2625–2629.

33. VizcainoJA, CoteRG, CsordasA, DianesJA, FabregatA, et al. (2013) The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013. Nucleic Acids Res 41: D1063–1069.