Heat Avoidance Is Regulated by Transient Receptor Potential (TRP) Channels and a Neuropeptide Signaling Pathway in Caenorhabditis elegans
Heat Avoidance Is Regulated by Transient Receptor Potential (TRP) Channels and a Neuropeptide Signaling Pathway in Caenorhabditis elegans
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DOI：
10.1534/genetics.111.127100
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发表时间：
2011-05-01
期刊：
影响因子：
3.3
通讯作者：
Goodman, Miriam B.
中科院分区：
文献类型：
--
作者：
Glauser, Dominique A.;Chen, Will C.;Goodman, Miriam B.
避免极端炎热和寒冷的能力对生存至关重要，这取决于热痛觉。瞬时受体电位（TRP）通道的TRPV亚群是热激活的，被认为在脊椎动物和果蝇中负责热探测。为了深入了解热痛觉的遗传和神经基础，我们开发了量化秀丽隐杆线虫（Caenorhabditis elegans）的有害热回避的分析，并利用它们来研究这种行为的遗传基础。首先，我们筛选了18个TRP通道基因（包括所有TRPV同源基因）的突变体，在单突变体和选择的双突变体和三突变体中只发现了轻微的热回避缺陷，这表明其他基因参与了其中。接下来，我们比较了两个在热回避阈值上存在差异的秀丽隐杆线虫的野生分离株，并将这种表型变异与神经肽受体基因npr-1的多态性联系起来。进一步的分析表明，无论是NPR-1受体还是其配体FLP-21的缺失，都增加了热回避的阈值。细胞特异性的nrpr -1的拯救与调节热回避回路中的中间神经元RMG有关。这种神经肽信号通路独立于TRPV基因osm-9和ocr-2，因为缺乏npr-1和两个TRPV通道的突变体比只缺乏npr-1或同时缺乏osm-9和ocr-2的突变体在热回避方面存在更严重的缺陷。我们的研究结果表明，TRPV通道和FLP-21/NPR-1神经肽信号通路决定了秀丽隐杆线虫的热回避阈值。
The ability to avoid noxious extremes of hot and cold is critical for survival and depends on thermal nociception. The TRPV subset of transient receptor potential (TRP) channels is heat activated and proposed to be responsible for heat detection in vertebrates and fruit flies. To gain insight into the genetic and neural basis of thermal nociception, we developed assays that quantify noxious heat avoidance in the nematode Caenorhabditis elegans and used them to investigate the genetic basis of this behavior. First, we screened mutants for 18 TRP channel genes (including all TRPV orthologs) and found only minor defects in heat avoidance in single and selected double and triple mutants, indicating that other genes are involved. Next, we compared two wild isolates of C. elegans that diverge in their threshold for heat avoidance and linked this phenotypic variation to a polymorphism in the neuropeptide receptor gene npr-1. Further analysis revealed that loss of either the NPR-1 receptor or its ligand, FLP-21, increases the threshold for heat avoidance. Cell-specific rescue of npr-1 implicates the interneuron RMG in the circuit regulating heat avoidance. This neuropeptide signaling pathway operates independently of the TRPV genes, osm-9 and ocr-2, since mutants lacking npr-1 and both TRPV channels had more severe defects in heat avoidance than mutants lacking only npr-1 or both osm-9 and ocr-2. Our results show that TRPV channels and the FLP-21/NPR-1 neuropeptide signaling pathway determine the threshold for heat avoidance in C. elegans.