論文 - 詳細
| RRC ID | 86722 |
|---|---|
| 著者 | Gao G, Guo S, Zhang Q, Zhang H, Zhang C, Peng G. |
| タイトル | Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles. |
| ジャーナル | Elife |
| Abstract |
Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of Kiaa1024L/Minar2, a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of kiaa1024L/minar2 causes hearing loss in the zebrafish. Defects in mechanotransduction, longer and thinner hair bundles, and enlarged apical lysosomes in hair cells are observed in the kiaa1024L/minar2 mutant. In cultured cells, Kiaa1024L/Minar2 is mainly localized to lysosomes, and its overexpression recruits cholesterol and increases cholesterol labeling. Strikingly, cholesterol is highly enriched in the hair bundle membrane, and loss of kiaa1024L/minar2 reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the kiaa1024L/minar2 mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing. |
| 巻・号 | 11 |
| 公開日 | 2022-11-1 |
| DOI | 10.7554/eLife.80865 |
| PII | 80865 |
| PMID | 36317962 |
| PMC | PMC9714970 |
| MeSH | Animals Cholesterol / metabolism Hearing / physiology Hearing Loss* / genetics Mechanotransduction, Cellular* / genetics Mechanotransduction, Cellular* / physiology Membrane Proteins Stereocilia / genetics Stereocilia / metabolism Zebrafish* / physiology Zebrafish Proteins / genetics |
| IF | 7.08 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 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 | |
| ゼブラフィッシュ | UAS:GFP |