David C Klein

Publications (186) View all

• Article: RGS2 is a Feedback Inhibitor of Melatonin Production in the Pineal Gland

  M. Matsuo, S. L. Coon, D. C. Klein
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  ABSTRACT: The 24-hour rhythmic production of melatonin by the pineal gland is essential for coordinating circadian physiology. Melatonin production increases at night in response to the release of norepinephrine from sympathetic nerve processes which innervate the pineal gland. This signal is transduced through G-protein-coupled adrenergic receptors. Here, we found that the abundance of Regulator of G-protein Signaling 2 (RGS2) increases at night, that expression is increased by norepinephrine and that this protein has a negative feedback effect on melatonin production. These data are consistent with the conclusion that RGS2 functions on a daily basis to negatively modulate melatonin production.
  FEBS Lett. 01/2013;
• Article: Global daily dynamics of the mineal transcriprome

  D.M. Bustos, M.J. Bailey, D. Sugden, D.A. Carter, M.F. Rath, M. Møller, S.L. Coon, J.L. Weller, D.C. Klein
  Cell.Tissue Res. 01/2011; 344:1-11.
• Source

  Available from: Jack Falcón

  Article: Transcriptional regulation of arylalkylamine-N-acetyltransferase-2 gene in the pineal gland of the gilthead seabream.

  B Zilberman-Peled, L Appelbaum, D Vallone, N S Foulkes, S Anava, A Anzulovich, S L Coon, D C Klein, J Falcón, B Ron, Y Gothilf
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  ABSTRACT: Pineal serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase; AANAT) is considered the key enzyme in the generation of circulating melatonin rhythms; the rate of melatonin production is determined by AANAT activity. In all the examined species, AANAT activity is regulated at the post-translational level and, to a variable degree, also at the transcriptional level. Here, the transcriptional regulation of pineal aanat (aanat2) of the gilthead seabream (Sparus aurata) was investigated. Real-time polymerase chain reaction quantification of aanat2 mRNA levels in the pineal gland collected throughout the 24-h cycle revealed a rhythmic expression pattern. In cultured pineal glands, the amplitude was reduced, but the daily rhythmic expression pattern was maintained under constant illumination, indicating a circadian clock-controlled regulation of seabream aanat2. DNA constructs were prepared in which green fluorescent protein was driven by the aanat2 promoters of seabream and Northern pike. In vivo transient expression analyses in zebrafish embryos indicated that these promoters contain the necessary elements to drive enhanced expression in the pineal gland. In the light-entrainable clock-containing PAC-2 zebrafish cell line, a stably transfected seabream aanat2 promoter-luciferase DNA construct exhibited a clock-controlled circadian rhythm of luciferase activity, characteristic for an E-box-driven expression. In NIH-3T3 cells, the seabream aanat2 promoter was activated by a synergistic action of BMAL/CLOCK and orthodenticle homeobox 5 (OTX5). Promoter sequence analyses revealed the presence of the photoreceptor conserved element and an extended E-box (i.e. the binding sites for BMAL/CLOCK and OTX5 that have been previously associated with pineal-specific and rhythmic gene expression). These results suggest that seabream aanat2 is a clock-controlled gene that is regulated by conserved mechanisms.
  Journal of Neuroendocrinology 02/2007; 19(1):46-53. · 3.14 Impact Factor
• Source

  Available from: P. Michael Iuvone

  Chapter: Melatonin Biosynthesis in Chicken Retina

  P. M. Iuvone, N. W. Chong, M. Bernard, A. D. Brown, K. B. Thomas, D. C. Klein
  04/2006: pages 31-41;
• Source

  Available from: Jack Falcón

  Article: Genetic, temporal and developmental differences between melatonin rhythm generating systems in the teleost fish pineal organ and retina.

  J Falcón, Y Gothilf, S L Coon, G Boeuf, D C Klein
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  ABSTRACT: Complete melatonin rhythm generating systems, including photodetector, circadian clock and melatonin synthesis machinery, are located within individual photoreceptor cells in two sites in Teleost fish: the pineal organ and retina. In both, light regulates daily variations in melatonin secretion by controlling the activity of arylalkylamine N-acetyltransferase (AANAT). However, in each species examined to date, marked differences exist between the two organs which may involve the genes encoding the photopigments, genes encoding AANAT, the times of day at which AANAT activity and melatonin production peak and the developmental schedule. We review the fish pineal and retinal melatonin rhythm generating systems and consider the evolutional pressures and other factors which led to these differences.
  Journal of Neuroendocrinology 05/2003; 15(4):378-82. · 3.14 Impact Factor