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首页> 外文期刊>Journal of Neurophysiology >Picrotoxin dramatically speeds the mammalian circadian clock independent of Cys-loop receptors
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Picrotoxin dramatically speeds the mammalian circadian clock independent of Cys-loop receptors

机译：皮质毒素大大加速了哺乳动物昼夜时钟，独立于Cys-Loop受体

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摘要

Picrotoxin is extensively and specifically used to inhibit GABAA receptors and other members of the Cys-loop receptor superfamily. We find that picrotoxin acts independently of known Cys-loop receptors to shorten the period of the circadian clock markedly by specifically advancing the accumulation of PERIOD2 protein. We show that this mechanism is surprisingly tetrodotoxin-insensitive, and the effect is larger than any known chemical or genetic manipulation. Notably, our results indicate that the circadian target of picrotoxin is common to a variety of human and rodent cell types but not Drosophila, thereby ruling out all conserved Cys-loop receptors and known regulators of mammalian PERIOD protein stability. Given that the circadian clock modulates significant aspects of cell physiology including synaptic plasticity, these results have immediate and broad experimental implications. Furthermore, our data point to the existence of an important and novel target within the mammalian circadian timing system.
机译：微微毒素广泛，专门用于抑制加巴纳受体和其他成员的Cys-Loop受体超家族。我们发现皮质毒素独立于已知的Cys-Loop受体行动，通过特异性地推动蛋白质的积累来缩短昼夜节点的时期。我们表明这种机制令人惊讶的是肺毒素不敏感，效果大于任何已知的化学或遗传操作。值得注意的是，我们的结果表明，野生毒素的昼夜昼夜毒性靶是一种人类和啮齿动物细胞类型，而不是果蝇，从而统治所有保守的伴随蛋白质蛋白质蛋白质稳定性的已知调节因子。鉴于昼夜节拍时钟调节细胞生理学的显着方面，包括突触可塑性，这些结果具有即时和广泛的实验影响。此外，我们的数据指向哺乳动物昼夜时序系统内的重要和新的目标存在。

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