論文 - 詳細
| RRC ID | 46223 |
|---|---|
| 著者 | Wang D, O'Halloran D, Goodman MB. |
| タイトル | 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. |
| ジャーナル | J Gen Physiol |
| Abstract |
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. |
| 巻・号 | 142(4) |
| ページ | 437-49 |
| 公開日 | 2013-10-1 |
| DOI | 10.1085/jgp.201310959 |
| PII | jgp.201310959 |
| PMID | 24081984 |
| PMC | PMC3787776 |
| MeSH | Action Potentials Adaptation, Physiological Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclic GMP / metabolism Cyclic Nucleotide Phosphodiesterases, Type 2 / genetics Cyclic Nucleotide Phosphodiesterases, Type 2 / metabolism* Cyclic Nucleotide-Gated Cation Channels / metabolism Guanylate Cyclase / genetics Guanylate Cyclase / metabolism* Locomotion Mutation Neuronal Calcium-Sensor Proteins / genetics Neuronal Calcium-Sensor Proteins / metabolism* Neuropeptides / genetics Neuropeptides / metabolism* Signal Transduction* Thermoreceptors / metabolism* Thermoreceptors / physiology Thermosensing* |
| IF | 3.628 |
| 引用数 | 22 |
| WOS 分野 | PHYSIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3765 tm3098 tm1998 tm3617 |