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

Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus.
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DOI:
10.1038/ncomms1316
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发表时间:
2011
影响因子:
16.6
通讯作者:
Okamura, Hitoshi
Okamura, Hitoshi
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Doi, Masao;Ishida, Atsushi;Miyake, Akiko;Sato, Miho;Komatsu, Rie;Yamazaki, Fumiyoshi;Kimura, Ikuo;Tsuchiya, Soken;Kori, Hiroshi;Seo, Kazuyuki;Yamaguchi, Yoshiaki;Matsuo, Masahiro;Fustin, Jean-Michel;Tanaka, Rina;Santo, Yasuko;Yamada, Hiroyuki;Takahashi, Yukari;Araki, Michihiro;Nakao, Kazuki;Aizawa, Shinichi;Kobayashi, Masaki;Obrietan, Karl;Tsujimoto, Gozoh;Okamura, Hitoshi

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作为昼夜节律中心的视交叉上核(SCN)中数千个细胞时钟的同步振荡,是通过精确定时的细胞间通讯来协调的,其原理在很大程度上是未知的。在这里,我们表明RGS16(G蛋白信号转导16的调节器)的数量,一种已知的灭活GαI的蛋白质,在一个选择性的昼夜时间增加,以允许在SCN中依赖于时间的细胞内循环AMP信号的激活。去除RGS16基因会导致cAMP昼夜节律的丧失,从而延长行为节律的昼夜节律周期。时钟控制的RGS16对cAMP信号的时间精确调节是背内侧SCN维持与腹外侧SCN的正常相位关系所必需的。因此,依赖于RGS16的细胞内G蛋白信号的时间调节协调了SCN起搏神经元的细胞间同步性,从而定义了24 h的行为节律。昼夜节律由视交叉上核控制,控制节律的机制在很大程度上还没有被发现。在这项研究中,G蛋白调节因子Rgs16参与了视交叉上核维持节律所需的环状AMP的产生
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. Circadian rhythm is controlled by the suprachiasmatic nucleus and the mechanisms that control the rhythm are largely undiscovered. In this study, a G protein regulator, RGS16, is shown to be involved in the production of cyclic AMP that is required for the suprachiasmatic nucleus to maintain rhythm
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