Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF.
Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF.
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DOI：
10.1371/journal.pgen.1006346
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发表时间：
2016-09
期刊：
影响因子：
4.5
通讯作者：
Wegener C
中科院分区：
文献类型：
--
作者：
Chen J;Reiher W;Hermann-Luibl C;Sellami A;Cognigni P;Kondo S;Helfrich-Förster C;Veenstra JA;Wegener C
进食和睡眠是具有显著相互联系和交叉调节的基本行为。昼夜节律系统和肽能信号是这种调制的重要组成部分，但人们对它们相互作用以调节摄食和睡眠的机制和网络知之甚少。我们发现在果蝇中，表达Allatostatin A(ASTA)的多肽能PLP神经元和肠内分泌细胞的特异性产热激活减少了摄食并促进了睡眠。Asta细胞的激活效应是由Asta多肽介导的，其受体与脊椎动物的甘丙肽受体同源，具有类似的和明显保守的功能。我们进一步确定PLP神经元是神经肽色素分散因子(PDF)的下游目标，神经肽色素分散因子是生物钟的输出因子。PLP神经元与表达PDF的时钟神经元接触，cAMP成像显示PLP神经元表达功能性的PDF受体。沉默Asta信号，并通过拴系的PDF持续输入Asta细胞，会以相反的方向改变睡眠/活动比率，但不影响节律性。综上所述，我们的结果表明，通过不同的神经元和内分泌Asta细胞亚群发出的多效性Asta信号使果蝇适应可被PDF调节的消化节能状态。进食和睡眠是受不同神经肽控制的基本行为。虽然进食与清醒时间有关，但睡眠会阻止进食。进食和睡眠都是通过体内生物钟在一天中的特定时间段进行定时的，大概是为了优化行为和新陈代谢过程。我们研究了果蝇体内Allatostatin A(AstA)多肽的功能。AstA由中肠上皮中的神经元和内分泌细胞产生。大脑和中肠中产生Asta的细胞亚群的热激活表明，Asta以相反的方向影响摄食和睡眠：摄食因Asta信号而减少，而睡眠则促进。其他人之前可能表明，昆虫Asta还抑制肠道运动和肠道消化酶的释放。一个吸引人的结论是，ASTA信号有助于将果蝇置于消化节能状态。有趣的是，一组六个表达ASTA的PLP神经元与生物钟网络中心的神经元密切接触，并表达时钟输出信号PDF的功能受体。这开启了PLP神经元处于时钟、进食和睡眠之间的界面的可能性--这一假说需要在未来得到验证。
Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF. Feeding and sleep are fundamental behaviours that are controlled by diverse neuropeptides. While feeding is associated with wake periods, sleep prevents feeding. Both feeding and sleep are timed to specific parts of the day by internal clocks, presumably to optimise behaviour and metabolic processes. We investigated the functions of Allatostatin A (AstA) peptides in the fruit fly. AstA is produced by neurons as well as by endocrine cells in the midgut epithelium. Thermogenetic activation of subsets of AstA-producing cells in the brain and midgut revealed that AstA affects both feeding and sleep in opposite directions: feeding is reduced by AstA signalling, while sleep is promoted. Others could previously show that insect AstA also inhibits gut motility and release of digestive enzymes from the gut. An attractive conclusion is that AstA signalling helps to put flies in a digestive energy-saving state. Interestingly, a set of six AstA-expressing PLP neurons are in close contact to neurons central to the circadian clock network, and express functional receptors for the clock output signal PDF. This opens the possibility that PLP neurons are at the interface between clock, feeding and sleep—a hypothesis that needs to be tested in the future.
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影响因子：
3
作者：
Brown JA;Woodworth HL;Leinninger GM
通讯作者：
Leinninger GM
影响因子：
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