Pickpocket is a DEG/ENaC protein required for mechanical nociception in Drosophila larvae.

Pickpocket is a DEG/ENaC protein required for mechanical nociception in Drosophila larvae.
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DOI:
10.1016/j.cub.2009.12.057
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发表时间:
2010-03-09
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Tracey WD
Tracey WD
中科院分区:
其他
文献类型:
--
作者:
Zhong L;Hwang RY;Tracey WD

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果蝇幼虫的高度分支的IV类多树突感觉神经元作为多模态伤害感受器起作用,其是对有害热(>39°C)或有害机械(>30 mN)刺激的行为反应所必需的。然而,使这些细胞能够检测热和力的分子机制尚不清楚。在这里,我们报告的扒手(ppk)基因,它编码的变性蛋白/上皮钠通道(DEG/ENaC)亚基,需要机械伤害,但不是热伤害在这些感觉细胞。扒窃的Lartarus突变体在对苛刻的机械刺激的反应中表现出大大降低的伤害感受行为。然而,扒手突变体对轻轻触摸表现出正常的行为反应。组织特异性敲除伤害感受器中的pickpocket表型模仿机械伤害感受损伤,而不引起热伤害感受行为的缺陷。最后,光遗传学触发的伤害感受行为不受pickpocket RNAi的影响,这表明ppk通常不是伤害感受器的兴奋性所需的。有趣的是,已知DEG/ENaCs在检测C中的温和触摸刺激中起关键作用。在哺乳动物中,也涉及粗糙触觉的某些方面。我们的研究结果表明,果蝇中检测粗糙触摸的神经元利用类似的机械感觉分子。
Highly branched Class IV multidendritic sensory neurons of the Drosophila larva function as polymodal nociceptors that are necessary for behavioral responses to noxious heat (>39°C) or noxious mechanical (>30 mN) stimuli. However, the molecular mechanisms that allow these cells to detect both heat and force are unknown. Here, we report that the pickpocket(ppk) gene, which encodes a Degenerin/ Epithelial Sodium Channel (DEG/ENaC) subunit, is required for mechanical nociception but not thermal nociception in these sensory cells. Larvae mutant for pickpocket show greatly reduced nociception behaviors in response to harsh mechanical stimuli. However, pickpocket mutants display normal behavioral responses to gentle touch. Tissue specific knockdown of pickpocket in nociceptors phenocopies the mechanical nociception impairment without causing defects in thermal nociception behavior. Finally, optogenetically-triggered nociception behavior is unaffected by pickpocket RNAi which indicates that ppk is not generally required for the excitability of the nociceptors. Interestingly, DEG/ENaCs are known to play a critical role in detecting gentle touch stimuli in C. elegans and have also been implicated in some aspects of harsh touch sensation in mammals. Our results suggest that neurons which detect harsh touch in Drosophila utilize similar mechanosensory molecules.
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