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

被引:106
作者
Doi, Masao [1 ]
Ishida, Atsushi [2 ]
Miyake, Akiko [2 ]
Sato, Miho [1 ]
Komatsu, Rie [1 ]
Yamazaki, Fumiyoshi [1 ]
Kimura, Ikuo [3 ]
Tsuchiya, Soken [3 ]
Kori, Hiroshi [4 ,5 ]
Seo, Kazuyuki [1 ]
Yamaguchi, Yoshiaki [1 ]
Matsuo, Masahiro [1 ]
Fustin, Jean-Michel [1 ]
Tanaka, Rina [1 ]
Santo, Yasuko [1 ]
Yamada, Hiroyuki [1 ]
Takahashi, Yukari [1 ]
Araki, Michihiro [6 ]
Nakao, Kazuki [7 ]
Aizawa, Shinichi [7 ]
Kobayashi, Masaki [8 ]
Obrietan, Karl [9 ]
Tsujimoto, Gozoh [3 ]
Okamura, Hitoshi [1 ]
机构
[1] Kyoto Univ, Dept Syst Biol, Grad Sch Pharmaceut Sci, Kyoto 6068501, Japan
[2] Kobe Univ, Grad Sch Med, Div Mol Brain Sci, Kobe, Hyogo 6500017, Japan
[3] Kyoto Univ, Dept Genom Drug Discovery Sci, Grad Sch Pharmaceut Sci, Kyoto 6068501, Japan
[4] Ochanomizu Univ, Ochadai Acad Prod, Div Adv Sci, Tokyo 1128610, Japan
[5] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
[6] Kyoto Univ, Educ Unit Global Leaders, Kyoto 6068501, Japan
[7] Riken Ctr Dev Biol, Lab Anim Resources & Genet Engn, Kobe, Hyogo 6500047, Japan
[8] Tohoku Inst Technol, Dept Elect, Sendai, Miyagi 9828577, Japan
[9] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA
关键词
GENE-EXPRESSION; RESPONSE ELEMENT; CLOCK; MOUSE; TRANSCRIPTION; LIGHT; HYPOTHALAMUS; OSCILLATOR; INHIBITION; PROMOTERS;
D O I
10.1038/ncomms1316
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Gai, 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.
引用
收藏
页数:9
相关论文
共 60 条
[1]   Molecular mechanism of cell-autonomous circadian gene expression of Period2, a crucial regulator of the mammalian circadian clock [J].
Akashi, M ;
Ichise, T ;
Mamine, T ;
Takumi, T .
MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (02) :555-565
[2]  
Akiyama M, 1999, J NEUROSCI, V19, P1115
[3]   GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons [J].
Aton, Sara J. ;
Huettner, James E. ;
Straume, Martin ;
Herzog, Erik D. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (50) :19188-19193
[4]   Come together, right...now: Synchronization of rhythms in a mammalian circadian clock [J].
Aton, SJ ;
Herzog, ED .
NEURON, 2005, 48 (04) :531-534
[5]   Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons [J].
Aton, SJ ;
Colwell, CS ;
Harmar, AJ ;
Waschek, J ;
Herzog, ED .
NATURE NEUROSCIENCE, 2005, 8 (04) :476-483
[6]   Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts [J].
Balsalobre, A ;
Marcacci, L ;
Schibler, U .
CURRENT BIOLOGY, 2000, 10 (20) :1291-1294
[7]   R4 RGS proteins: Regulation of G-protein signaling and beyond [J].
Bansal, Geetanjall ;
Druey, Kirk M. ;
Xie, Zhihui .
PHARMACOLOGY & THERAPEUTICS, 2007, 116 (03) :473-495
[8]  
Beadling C, 1999, J IMMUNOL, V162, P2677
[9]   Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition of intracellular cAMP content [J].
Chabardès, D ;
Imbert-Teboul, M ;
Elalouf, JM .
CELLULAR SIGNALLING, 1999, 11 (09) :651-663
[10]   Characterization of a novel mammalian RGS protein that binds to G alpha proteins and inhibits pheromone signaling in yeast [J].
Chen, CH ;
Zheng, B ;
Han, JH ;
Lin, SC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (13) :8679-8685