{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gao G"],"funding":["Shanghai Municipal Science and Technology Commission","National Natural Science Foundation of China","National Key Research and Development Program of China"],"pagination":["e80865"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9714970"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11"],"pubmed_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 <i>Kiaa1024L</i>/<i>Minar2</i>, a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of <i>kiaa1024L/minar2</i> 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 <i>kiaa1024L/minar2</i> 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 <i>kiaa1024L/minar2</i> reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the <i>kiaa1024L/minar2</i> mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing."],"journal":["eLife"],"pubmed_title":["Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles."],"pmcid":["PMC9714970"],"funding_grant_id":["2018YFA0801000","31571067","Major Project No.2018SHZDZX01"],"pubmed_authors":["Peng G","Zhang H","Gao G","Guo S","Zhang C","Zhang Q"],"additional_accession":[]},"is_claimable":false,"name":"Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles.","description":"Unbiased genetic screens implicated a number of uncharacterized genes in hearing loss, suggesting some biological processes required for auditory function remain unexplored. Loss of <i>Kiaa1024L</i>/<i>Minar2</i>, a previously understudied gene, caused deafness in mice, but how it functioned in the hearing was unclear. Here, we show that disruption of <i>kiaa1024L/minar2</i> 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 <i>kiaa1024L/minar2</i> 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 <i>kiaa1024L/minar2</i> reduces cholesterol localization to the hair bundles. Lowering cholesterol levels aggravates, while increasing cholesterol levels rescues the hair cell defects in the <i>kiaa1024L/minar2</i> mutant. Therefore, cholesterol plays an essential role in hair bundles, and Kiaa1024L/Minar2 regulates cholesterol distribution and homeostasis to ensure normal hearing.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-19T03:31:49.693Z","creation":"2025-04-07T13:41:42.302Z"},"accession":"S-EPMC9714970","cross_references":{"pubmed":["36317962"],"doi":["10.7554/eLife.80865"]}}