Reference - Detail
| RRC ID | 86722 |
|---|---|
| Author | Gao G, Guo S, Zhang Q, Zhang H, Zhang C, Peng G. |
| Title | Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles. |
| Journal | 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. |
| Volume | 11 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Zebrafish | UAS:GFP |