GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent thermotransduction cascade in the AFD neurons responsible for C. elegans thermotaxis.
GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent thermotransduction cascade in the AFD neurons responsible for C. elegans thermotaxis.
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DOI：
10.1085/jgp.201310959
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Goodman MB
中科院分区：
文献类型：
--
作者：
Wang D;O'Halloran D;Goodman MB
某些温度感受器神经元对微小的温度波动(0.01℃或更低)很敏感，并通过适应过程在广泛的环境温度范围内保持其敏感性，但对这种表现的生化基础的了解还很初级。以往对秀丽线虫AFD热感受器的研究揭示了依赖于三个受体鸟苷环化酶(RGC)、GCY-8、GCY-18和GCY-23的信号级联，并产生由环状GMP门控离子通道携带的温敏性热感受器电流(ThRC)。ThrC的激活阈值通过未知的钙依赖过程适应环境温度。在这里，我们使用来自AFD的活体全细胞膜片钳记录来表明GCY-8的丢失，而不是GCY-18或GCY-23的丢失，减少或消除ThRCs，确定这种RGC是一个关键的信号元件。为了更多地了解热传导和适应，我们使用行为筛选和基因表达模式分析来鉴定可能有助于热传导的磷酸二酯酶(PDE)。删除PDE-2会使ThRC激活阈值与环境温度脱钩，从而改变适应。我们提供的证据表明，保守的神经元钙传感器1蛋白也调节ThRC激活的阈值，并提出了一个信号网络来解释ThRC的激活和适应。由于PDE在脊椎动物的光传导、嗅觉、血管收缩和心血管功能的调节等多种生物学过程中发挥着重要的作用，因此这项研究对于理解基于环核苷酸的信号网络是如何获得非凡的敏感性和动态范围具有广泛的意义。
Certain thermoreceptor neurons are sensitive to tiny thermal fluctuations (0.01°C or less) and maintain their sensitivity across a wide range of ambient temperatures through a process of adaptation, but understanding of the biochemical basis for this performance is rudimentary. Prior studies of the AFD thermoreceptor in Caenorhabditis elegans revealed a signaling cascade that depends on a trio of receptor guanylate cyclases (rGCs), GCY-8, GCY-18, and GCY-23, and gives rise to warming-activated thermoreceptor currents (ThRCs) carried by cyclic GMP–gated ion channels. The threshold for ThRC activation adapts to the ambient temperature through an unknown calcium-dependent process. Here, we use in vivo whole-cell patch-clamp recording from AFD to show that loss of GCY-8, but not of GCY-18 or GCY-23, reduces or eliminates ThRCs, identifying this rGC as a crucial signaling element. To learn more about thermotransduction and adaptation, we used behavioral screens and analysis of gene expression patterns to identify phosphodiesterases (PDEs) likely to contribute to thermotransduction. Deleting PDE-2 decouples the threshold for ThRC activation from ambient temperature, altering adaptation. We provide evidence that the conserved neuronal calcium sensor 1 protein also regulates the threshold for ThRC activation and propose a signaling network to account for ThRC activation and adaptation. Because PDEs play essential roles in diverse biological processes, including vertebrate phototransduction and olfaction, and regulation of smooth muscle contractility and cardiovascular function, this study has broad implications for understanding how extraordinary sensitivity and dynamic range is achieved in cyclic nucleotide–based signaling networks.
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DOI：
10.1016/j.cub.2009.12.006
发表时间：
2010-02-09
期刊：
Current biology : CB
影响因子：
--
作者：
Fain GL;Hardie R;Laughlin SB
通讯作者：
Laughlin SB
影响因子：
3.6
作者：
Burgoyne RD;Haynes LP
通讯作者：
Haynes LP
影响因子：
--
作者：
Goodman, Miriam B.;Lindsay, Theodore H.;Lockery, Shawn R.;Richmond, Janet E.
通讯作者：
Richmond, Janet E.
影响因子：
34.7
作者：
Burgoyne, Robert D.
通讯作者：
Burgoyne, Robert D.
影响因子：
3.3
作者：
Glauser, Dominique A.;Chen, Will C.;Goodman, Miriam B.
通讯作者：
Goodman, Miriam B.