Metabotropic GABA signalling modulates longevity in C. elegans.
Metabotropic GABA signalling modulates longevity in C. elegans.
复制标题
代谢型 GABA 信号传导可调节线虫的寿命。
DOI：
10.1038/ncomms9828
复制
发表时间：
2015-11-05
影响因子：
16.6
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Chun L;Gong J;Yuan F;Zhang B;Liu H;Zheng T;Yu T;Xu XZ;Liu J
神经系统在调节寿命方面起着重要的作用，但人们对此知之甚少。GABA是一种重要的抑制性神经递质，最为人所知的是调节各种生物体的神经系统功能和行为。然而，GABA信号是否影响衰老还没有被探索。在这里，我们研究了线虫中缺乏每一种主要神经递质的突变体，发现GABA信号的缺失延长了寿命。这种长寿效应是由代谢性GABAB受体GBB-1介导的，而不是电离性GABAA受体。GbB-1通过G蛋白-PLCβ信号传递长寿信号到转录因子DAF-16/FOXO来调节寿命，DAF-16/FOXO是寿命的关键调节因子。哺乳动物GABAB受体可以在功能上替代GBB-1在线虫寿命控制中的作用。我们的结果揭示了GABA信号在线虫寿命调节中的新作用，增加了在其他生物体中可能发生类似过程的可能性。线虫的神经系统影响着生物的寿命，但机制细节却鲜为人知。在这里，Chun等人。表明神经递质GABA通过作用于运动神经元上的GABAB受体来调节蠕虫的寿命，GABAB受体激活肠道中的转录因子DAF-16。
The nervous system plays an important but poorly understood role in modulating longevity. GABA, a prominent inhibitory neurotransmitter, is best known to regulate nervous system function and behaviour in diverse organisms. Whether GABA signalling affects aging, however, has not been explored. Here we examined mutants lacking each of the major neurotransmitters in C. elegans, and find that deficiency in GABA signalling extends lifespan. This pro-longevity effect is mediated by the metabotropic GABAB receptor GBB-1, but not ionotropic GABAA receptors. GBB-1 regulates lifespan through G protein-PLCβ signalling, which transmits longevity signals to the transcription factor DAF-16/FOXO, a key regulator of lifespan. Mammalian GABAB receptors can functionally substitute for GBB-1 in lifespan control in C. elegans. Our results uncover a new role of GABA signalling in lifespan regulation in C. elegans, raising the possibility that a similar process may occur in other organisms. The C. elegans nervous system influences organismal lifespan but mechanistic details are poorly understood. Here, Chun et al. show that the neurotransmitter GABA regulates worm lifespan by acting on GABAB receptors in motor neurons, which activate the transcription factor DAF-16 in the intestine.