Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus

Masao Doi, Atsushi Ishida, Akiko Miyake, Miho Sato, Rie Komatsu, Fumiyoshi Yamazaki, Ikuo Kimura, Soken Tsuchiya, Hiroshi Kori, Kazuyuki Seo, Yoshiaki Yamaguchi, Masahiro Matsuo, Jean-Michel Fustin, Rina Tanaka, Yasuko Santo, Hiroyuki Yamada, Yukari Takahashi, Michihiro Araki, Kazuki Nakao, Shinichi Aizawa, Masaki Kobayashi, Karl Obrietan, Gozoh Tsujimoto and Hitoshi Okamura ()
Additional contact information
Masao Doi: Graduate School of Pharmaceutical Sciences, Kyoto University
Atsushi Ishida: Graduate School of Medicine, Kobe University
Akiko Miyake: Graduate School of Medicine, Kobe University
Miho Sato: Graduate School of Pharmaceutical Sciences, Kyoto University
Rie Komatsu: Graduate School of Pharmaceutical Sciences, Kyoto University
Fumiyoshi Yamazaki: Graduate School of Pharmaceutical Sciences, Kyoto University
Ikuo Kimura: Graduate School of Pharmaceutical Sciences, Kyoto University
Soken Tsuchiya: Graduate School of Pharmaceutical Sciences, Kyoto University
Hiroshi Kori: Ochadai Academic Production, Ochanomizu University
Kazuyuki Seo: Graduate School of Pharmaceutical Sciences, Kyoto University
Yoshiaki Yamaguchi: Graduate School of Pharmaceutical Sciences, Kyoto University
Masahiro Matsuo: Graduate School of Pharmaceutical Sciences, Kyoto University
Jean-Michel Fustin: Graduate School of Pharmaceutical Sciences, Kyoto University
Rina Tanaka: Graduate School of Pharmaceutical Sciences, Kyoto University
Yasuko Santo: Graduate School of Pharmaceutical Sciences, Kyoto University
Hiroyuki Yamada: Graduate School of Pharmaceutical Sciences, Kyoto University
Yukari Takahashi: Graduate School of Pharmaceutical Sciences, Kyoto University
Michihiro Araki: Education Unit for Global Leaders, Kyoto University
Kazuki Nakao: Laboratory for Animal Resources and Genetic Engineering, Riken Center for Developmental Biology
Shinichi Aizawa: Laboratory for Animal Resources and Genetic Engineering, Riken Center for Developmental Biology
Masaki Kobayashi: Tohoku Institute of Technology
Karl Obrietan: The Ohio State University
Gozoh Tsujimoto: Graduate School of Pharmaceutical Sciences, Kyoto University
Hitoshi Okamura: Graduate School of Pharmaceutical Sciences, Kyoto University

Nature Communications, 2011, vol. 2, issue 1, 1-9

Abstract: Abstract Synchronous oscillations of thousands of cellular clocks in the suprachiasmatic nucleus (SCN), the circadian centre, are coordinated by precisely timed cell–cell communication, the principle of which is largely unknown. Here we show that the amount of RGS16 (regulator of G protein signalling 16), a protein known to inactivate Gαi, increases at a selective circadian time to allow time-dependent activation of intracellular cyclic AMP signalling in the SCN. Gene ablation of Rgs16 leads to the loss of circadian production of cAMP and as a result lengthens circadian period of behavioural rhythm. The temporally precise regulation of the cAMP signal by clock-controlled RGS16 is needed for the dorsomedial SCN to maintain a normal phase-relationship to the ventrolateral SCN. Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour.

Date: 2011
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DOI: 10.1038/ncomms1316

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