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Originally published In Press as doi:10.1074/jbc.M209241200 on October 29, 2002

J. Biol. Chem., Vol. 278, Issue 2, 718-723, January 10, 2003
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Ca2+/cAMP Response Element-binding Protein (CREB)-dependent Activation of Per1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock*

Shelley A. TischkauDagger §, Jennifer W. MitchellDagger , Sheue-Houy TyanDagger §, Gordon F. Buchanan||, and Martha U. GilletteDagger §||**

From the Departments of Dagger  Cell and Structural Biology, || Molecular and Integrative Physiology, and the § Neuroscience Program, University of Illinois at Urbana-Champaign, B107 CLSL, Urbana, Illinois 61801

Light is a prominent stimulus that synchronizes endogenous circadian rhythmicity to environmental light/dark cycles. Nocturnal light elevates mRNA of the Period1 (Per1) gene and induces long term state changes, expressed as phase shifts of circadian rhythms. The cellular mechanism for Per1 elevation and light-induced phase advance in the suprachiasmatic nucleus (SCN), a process initiated primarily by glutamatergic neurotransmission from the retinohypothalamic tract, was examined. Glutamate (GLU)-induced phase advances in the rat SCN were blocked by antisense oligodeoxynucleotide (ODN) against Per1 and Ca2+/cAMP response element (CRE)-decoy ODN. CRE-decoy ODN also blocked light-induced phase advances in vivo. Furthermore, the CRE-decoy blocked GLU-induced accumulation of Per1 mRNA. Thus, Ca2+/cAMP response element-binding protein (CREB) and Per1 are integral components of the pathway transducing light-stimulated GLU neurotransmission into phase advance of the circadian clock.


* This work was supported by United States Public Health Service Grants NS22155 and HL67007 (to M. U. G), NS10170 (to S. A. T.), NS11158 (to J. W. M.), and MH12351 (to G. F. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Current address: Dept. of Veterinary Biosciences, 3615 VMBSB, 2001 S. Lincoln Ave., Urbana, IL 61802.

** To whom correspondence should be addressed: Dept. of Cell & Structural Biology, University of Illinois, B107 CLSL, 601 S. Goodwin Ave., Urbana, IL 61801. Tel.: 217-244-1355; Fax: 217-333-4561; E-mail: mgillett@uiuc.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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