論文 - 詳細
| RRC ID | 5712 |
|---|---|
| 著者 | Kim H, Pierce-Shimomura JT, Oh HJ, Johnson BE, Goodman MB, McIntire SL. |
| タイトル | The dystrophin complex controls bk channel localization and muscle activity in Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| Abstract |
Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC components from humans to Caenorhabditis elegans suggest a similar molecular function. C. elegans DAPC mutants exhibit a unique locomotory deficit resulting from prolonged muscle excitation and contraction. Here we show that the C. elegans DAPC is essential for proper localization of SLO-1, the large conductance, voltage-, and calcium-dependent potassium (BK) channel, which conducts a major outward rectifying current in muscle under the normal physiological condition. Through analysis of mutants with the same phenotype as the DAPC mutants, we identified the novel islo-1 gene that encodes a protein with two predicted transmembrane domains. We demonstrate that ISLO-1 acts as a novel adapter molecule that links the DAPC to SLO-1 in muscle. We show that a defect in either the DAPC or ISLO-1 disrupts normal SLO-1 localization in muscle. Consistent with observations that SLO-1 requires a high calcium concentration for full activation, we find that SLO-1 is localized near L-type calcium channels in muscle, thereby providing a mechanism coupling calcium influx with the outward rectifying current. Our results indicate that the DAPC modulates muscle excitability by localizing the SLO-1 channel to calcium-rich regions of C. elegans muscle. |
| 巻・号 | 5(12) |
| ページ | e1000780 |
| 公開日 | 2009-12-1 |
| DOI | 10.1371/journal.pgen.1000780 |
| PMID | 20019812 |
| PMC | PMC2788698 |
| MeSH | Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium Dystrophin Dystrophin-Associated Protein Complex / physiology* Electrophysiology Large-Conductance Calcium-Activated Potassium Channels / genetics Large-Conductance Calcium-Activated Potassium Channels / metabolism* Muscles / physiology* Mutant Proteins |
| IF | 5.175 |
| 引用数 | 39 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | Patent(IFI CLAIMS) |
| 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 | tm2709 tm2737 |