Identification of guanylyl cyclases that function in thermosensory neurons of Caenorhabditis elegans

Identification of guanylyl cyclases that function in thermosensory neurons of Caenorhabditis elegans
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DOI:
10.1534/genetics.105.050013
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发表时间:
2006-04-01
期刊:
影响因子:
3.3
通讯作者:
Mori, I
Mori, I
中科院分区:
生物学2区
文献类型:
--
作者:
Inada, H;Ito, H;Mori, I

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秀丽隐杆线虫主要通过头部的AFD热感觉神经元来感知温度。对温度的响应可以观察为热梯度上的一种称为热趋向性的行为。研究表明,环核苷酸门控离子通道(CNG通道)在AFD的热感觉中起着关键作用。为了进一步确定AFD中的热感觉机制,我们试图通过反向遗传方法确定在CNG通道上游起作用的成分。遗传和行为分析表明,编码冠酰环化酶的gcy基因亚家族的三个成员(gcy-8、gcy-18和gcy-23)对线虫的趋热性至关重要。每个基因的启动子仅在AFD神经元中驱动报告基因的表达,并且标记蛋白定位于AFD的感觉末梢。每个gcy基因的单突变体表现出几乎正常的嗜热性。然而,携带这些基因的双重和三重突变的动物表现出有缺陷的趋热行为。通过在AFD神经元中表达三种gcy蛋白中的任何一种,可以挽救gcy三突变体的异常表型。这些结果表明,三种胍基环化酶在线虫的AFD神经元中具有冗余功能,介导了线虫的热感觉。
The nematode Caenorhabditis elegans senses temperature primarily via the AFD thermosensory neurons in the head. The response to temperature can be observed as a behavior called thermotaxis on thermal gradients. It has been shown that a cyclic nucleotide-gated ion channel (CNG channel) plays a critical role in thermosensation in AFD. To further identify the thermosensory mechanisms in AFD, we attempted to identify components that function upstream of the CNG channel by a reverse genetic approach. Genetic and behavioral analyses showed that three members of a subfamily of gcy genes (gcy-8, gcy-18, and gcy-23) encoding guanylyl cyclases were essential for thermotaxis in C. elegans. Promoters of each gene drove reporter gene expression exclusively in the AFD neurons and, moreover, tagged proteins were localized to the sensory endings of AFD. Single mutants of each gcy gene showed almost normal thermotaxis. However, animals carrying double and triple mutations in these genes showed defective thermotaxis behavior. The abnormal phenotype of the gcy triple mutants was rescued by expression of any one of the three GCY proteins in the AFD neurons. These results suggest that three guanylyl cyclases function redundantly in the AFD neurons to mediate thermosensation by C. elegans.