Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their...Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their roles in the stereocilia and auditory functions are not fully understood.Here,we identify Plscr5 as a downstream target of the transcription factor POU4F3 essential for hair cell function,whose mutation causes human DFNA15 deafness.Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss.Functional analyses reveal that PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes,particularly in inner hair cells,and is important for outer hair cell and stereocilia maintenance.Our findings highlight PLSCR5 as an important downstream effector of POU4F3 and regulator of phosphatidylserine externalization and membrane dynamics required for auditory functions.展开更多
基金supported by the National Natural Science Foundation of China(82171136 and 92368110 to G.W.,82201291 to G.-J.Z.,82192861 to Z.X.,81970884 and 82192862 to X.G.)the Natural Science Foundation of Jiangsu Province(BK20220188 to Q.L.,BK20220189 to G.-J.Z.)the Fundamental Research Funds for the Central Universities(021414380533 to G.W.).
文摘Hearing relies on the structural and functional integrity of cochlear hair cells,particularly their apical F-actin-filled stereocilia.Phospholipid scramblases are important for maintaining membrane asymmetry,but their roles in the stereocilia and auditory functions are not fully understood.Here,we identify Plscr5 as a downstream target of the transcription factor POU4F3 essential for hair cell function,whose mutation causes human DFNA15 deafness.Plscr5 knockout mice exhibit progressive hearing loss due to stereocilia degeneration and hair cell loss.Functional analyses reveal that PLSCR5 contributes to phosphatidylserine externalization in hair cell apical membranes,particularly in inner hair cells,and is important for outer hair cell and stereocilia maintenance.Our findings highlight PLSCR5 as an important downstream effector of POU4F3 and regulator of phosphatidylserine externalization and membrane dynamics required for auditory functions.
基金This work was supported by the National Natural Sciences Foundation of China (No.30471238)National "863 Project" (No.2003AA243051)Phenom Innovation Foundation of Henan Province(No.0521001900) and Sustainment Plan of Northwest A&F University for Topnotch Person with Ability.
