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, Hitoshi Okamura

Index: Nat. Commun. 2 , 327, (2011)

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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.© 2011 Macmillan Publishers Limited. All rights reserved.