Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates Circadian Clock Dynamics

Molecular Neurobiology
Tsvetan SerchovRolf Heumann

Abstract

Circadian rhythms, generated in the mouse suprachiasmatic nucleus (SCN), are synchronized to the environmental day-night changes by photic input. The activation of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) and cAMP response element-binding protein (CREB)-mediated transcription play a critical role in this photoentrainment. The small GTPase Ras is one of the major upstream regulators of the ERK1,2/CREB pathway. In contrast to the well-described role of Ras in structural and functional synaptic plasticity in the adult mouse brain, the physiological regulation of Ras by photic sensory input is yet unknown. Here, we describe for the first time a circadian rhythm of Ras activity in the mouse SCN. Using synRas transgenic mice, expressing constitutively activated V12-Ha-Ras selectively in neurons, we demonstrate that enhanced Ras activation causes shortening of the circadian period length. We found upregulated expression and decreased inhibitory phosphorylation of the circadian period length modulator, glycogen synthase kinase-3 beta (GSK3β), in the SCN of synRas mice. Conversely, downregulation of Ras activity by blocking its function with an antibody in oscillating cell cultures reduced protein levels and increased...Continue Reading

References

Mar 1, 1990·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·K TakahashiT Goto
Oct 1, 1994·Current Opinion in Neurobiology·R Heumann
Apr 1, 1996·Current Opinion in Cell Biology·C J Marshall
Feb 1, 1997·Current Opinion in Genetics & Development·M E Katz, F McCormick
Jun 11, 1999·The Journal of Biological Chemistry·K ObrietanD R Storm
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Zdenka Travnickova-BendovaPaolo Sassone-Corsi
Jun 4, 2002·The Journal of Biological Chemistry·Greg Q ButcherKarl Obrietan
Aug 29, 2002·Nature·Steven M Reppert, David R Weaver
Jan 22, 2003·Nature Neuroscience·Han S LeeMichael N Lehman
Apr 2, 2003·Molecular Neurobiology·Robert Waltereit, Michael Weller
May 20, 2003·The European Journal of Neuroscience·Heather DziemaKarl Obrietan
Mar 11, 2004·The European Journal of Neuroscience·Greg Q ButcherKarl Obrietan
Jun 9, 2004·The European Journal of Neuroscience·Thomas ArendtRolf Heumann
Aug 4, 2004·Journal of Neurochemistry·Andrew N Coogan, Hugh D Piggins
Sep 8, 2004·Journal of Neuroscience Research·Ulrich GärtnerThomas Arendt
Oct 14, 2004·Journal of Neural Transmission·G SeegerTh Arendt
Jan 27, 2005·Neuroreport·Ulrich GärtnerThomas Arendt
Jun 24, 2005·The Journal of Biological Chemistry·Chisato IitakaNorio Ishida
Jun 28, 2005·The Journal of Biological Chemistry·Yuko HaradaYoshitaka Fukada
May 12, 2006·Chronobiology International·Tsvetan Serchov, Rolf Heumann
May 2, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Makoto AkashiKoichi Node
Dec 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tsuyoshi HirotaSteve A Kay
Mar 6, 2010·Frontiers in Behavioral Neuroscience·Pauline LafenêtreRolf Heumann

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Citations

Dec 8, 2015·Biological Chemistry·Tsvetan SerchovKnut Biber
Jan 21, 2016·Chronobiology International·Klára HahnováZdeňka Bendová
Aug 9, 2016·Frontiers in Cell and Developmental Biology·Brian J Altman
Jun 27, 2017·Frontiers in Neurology·Tsvetan Serchov, Rolf Heumann
May 5, 2021·Biochemistry. Biokhimii︠a︡·Gregory A ShilovskyVladimir P Skulachev

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