PUBLICATION
Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles
- Authors
- Gao, G., Guo, S., Zhang, Q., Zhang, H., Zhang, C., Peng, G.
- ID
- ZDB-PUB-221102-4
- Date
- 2022
- Source
- eLIFE 11: (Journal)
- Registered Authors
- Peng, Gang, Zhang, Cuizhen, Zhang, Hefei
- Keywords
- cell biology, neuroscience, zebrafish
- MeSH Terms
-
- Animals
- Cholesterol
- Hearing/physiology
- Hearing Loss*/genetics
- Mechanotransduction, Cellular/physiology
- Mice
- Zebrafish*/physiology
- Zebrafish Proteins/genetics
- PubMed
- 36317962 Full text @ Elife
Citation
Gao, G., Guo, S., Zhang, Q., Zhang, H., Zhang, C., Peng, G. (2022) Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles. eLIFE. 11:.
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 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 hair cell defects in kiaa1024L/minar2 mutant. Therefore cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping