The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

Sihao Gong; Qing Liu; Haibo Du; Linqing Zhang; Chengwen Zhu; Zhigang Xu; Xia Gao; Guang-Jie Zhu; Guoqiang Wan

doi:10.1016/j.jgg.2025.03.003

The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

doi: 10.1016/j.jgg.2025.03.003

Sihao Gong^a,b,
Qing Liu^a,b,c,
Haibo Du^d,
Linqing Zhang^a,b,
Chengwen Zhu^a,c,
Zhigang Xu^d,
Xia Gao^a,c, ,,
Guang-Jie Zhu^a,c, ,,
Guoqiang Wan^a,b,c, ,

a. MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China;
b. State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, Jiangsu 210008, China;
c. Research Institute of Otolaryngology, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China;
d. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China

基金项目:

This work is 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.), and the Fundamental Research Funds for the Central Universities (021414380533 to G. W.).

详细信息

通讯作者:
Xia Gao,E-mail:gaoxia@nju.edu.cn

Guang-Jie Zhu,E-mail:zhuzhugj@163.com

Guoqiang Wan,E-mail:guoqiangwan@nju.edu.cn

计量
- 文章访问数: 6
- HTML全文浏览量: 3
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2024-11-27
- 录用日期: 2025-03-04
- 修回日期: 2025-03-02
- 网络出版日期: 2025-07-11

The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

Sihao Gong^a,b,
Qing Liu^a,b,c,
Haibo Du^d,
Linqing Zhang^a,b,
Chengwen Zhu^a,c,
Zhigang Xu^d,
Xia Gao^{a,c
, ,},
Guang-Jie Zhu^{a,c
, ,},
Guoqiang Wan^{a,b,c
, ,}

a. MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School and the Model Animal Research Center of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China;
b. State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, National Resource Center for Mutant Mice of China, Nanjing University, Nanjing, Jiangsu 210008, China;
c. Research Institute of Otolaryngology, No. 321 Zhongshan Road, Nanjing, Jiangsu 210008, China;
d. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, China

Funds:

摘要

摘要:
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 PS externalization and membrane dynamics required for auditory functions.
- POU4F3 /
- PLSCR5 /
- Phospholipid scramblase /
- Hair cell /
- Hearing loss /
- Stereocilia /
- Phosphatidylserine
Abstract:
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 PS externalization and membrane dynamics required for auditory functions.
- POU4F3 /
- PLSCR5 /
- Phospholipid scramblase /
- Hair cell /
- Hearing loss /
- Stereocilia /
- Phosphatidylserine

HTML全文

参考文献(0)

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 6
HTML全文浏览量: 3
PDF下载量: 0
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

doi: 10.1016/j.jgg.2025.03.003

通讯作者:
Xia Gao,E-mail:gaoxia@nju.edu.cn

Guang-Jie Zhu,E-mail:zhuzhugj@163.com

Guoqiang Wan,E-mail:guoqiangwan@nju.edu.cn

计量

The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

计量

目录

留言板

The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

doi: 10.1016/j.jgg.2025.03.003

通讯作者: Xia Gao,E-mail:gaoxia@nju.edu.cn Guang-Jie Zhu,E-mail:zhuzhugj@163.com Guoqiang Wan,E-mail:guoqiangwan@nju.edu.cn

计量

出版历程

The phospholipid scramblase PLSCR5 is regulated by POU4F3 and required for hair cell stereocilia homeostasis and auditory functions

计量

出版历程

目录

通讯作者:
Xia Gao,E-mail:gaoxia@nju.edu.cn

Guang-Jie Zhu,E-mail:zhuzhugj@163.com

Guoqiang Wan,E-mail:guoqiangwan@nju.edu.cn