Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles

Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of / , a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, w...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2022-11, Vol.11
Main Authors: Gao, Ge, Guo, Shuyu, Zhang, Quan, Zhang, Hefei, Zhang, Cuizhen, Peng, Gang
Format: Article
Language:English
Subjects:
Animals
apical membrane
Auditory system
Cell Biology
Cholesterol
Cholesterol - metabolism
Deafness
Ears & hearing
Genes
Genetic screening
Genomes
Hair
hair bundle
hair cell
Hair cells
hearing
Hearing - physiology
Hearing loss
Hearing Loss - genetics
Homeostasis
Localization
Lysosomes
Mechanotransduction
Mechanotransduction, Cellular - genetics
Mechanotransduction, Cellular - physiology
Membranes
Mutants
Neuroscience
Physiology
Proteins
Stereocilia - genetics
Stereocilia - metabolism
Ubtor
Zebrafish - physiology
Zebrafish Proteins - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of / , a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of 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 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 reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.80865