論文 - 詳細
| RRC ID | 51496 |
|---|---|
| 著者 | Topalidou I, Cooper K, Pereira L, Ailion M. |
| タイトル | Dopamine negatively modulates the NCA ion channels in C. elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels. |
| 巻・号 | 13(10) |
| ページ | e1007032 |
| 公開日 | 2017-10-1 |
| DOI | 10.1371/journal.pgen.1007032 |
| PII | PGENETICS-D-16-02860 |
| PMID | 28968387 |
| PMC | PMC5638609 |
| MeSH | Acetylcholine / metabolism Animals Caenorhabditis elegans / drug effects* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Dopamine / pharmacology* Epistasis, Genetic G-Protein-Coupled Receptor Kinases / genetics G-Protein-Coupled Receptor Kinases / metabolism* GTP-Binding Protein alpha Subunits, Gi-Go / genetics GTP-Binding Protein alpha Subunits, Gi-Go / metabolism Gene Expression Regulation Genome-Wide Association Study Interneurons / drug effects Interneurons / metabolism Ion Channels / genetics Ion Channels / metabolism* Mixed Function Oxygenases / genetics Mixed Function Oxygenases / metabolism Promoter Regions, Genetic Receptors, Dopamine D2 / genetics Receptors, Dopamine D2 / metabolism Signal Transduction |
| IF | 5.175 |
| 引用数 | 9 |
| 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 | 8 |
| 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 | tm775 |