FCHSD2 is required for stereocilia maintenance in mouse cochlear hair cells

Author:

Zhai Xiaoyan1ORCID,Du Haibo1,Shen Yuxin1,Zhang Xiujuan1,Chen Zhengjun23,Wang Yanfei1,Xu Zhigang14ORCID

Affiliation:

1. , School of Life Sciences, Shandong University 1 Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education , Qingdao, Shandong 266237 , China

2. , Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS) 2 State Key Laboratory of Cell Biology , Shanghai 200031 , China

3. School of Life Science and Technology, ShanghaiTech University 3 , Shanghai 200031 , China

4. , Shandong Normal University 4 Shandong Provincial Collaborative Innovation Center of Cell Biology , Jinan, Shandong 250014 , China

Abstract

ABSTRACT Stereocilia are F-actin-based protrusions on the apical surface of inner-ear hair cells and are indispensable for hearing and balance perception. The stereocilia of each hair cell are organized into rows of increasing heights, forming a staircase-like pattern. The development and maintenance of stereocilia are tightly regulated, and deficits in these processes lead to stereocilia disorganization and hearing loss. Previously, we showed that the F-BAR protein FCHSD2 is localized along the stereocilia of cochlear hair cells and cooperates with CDC42 to regulate F-actin polymerization and cell protrusion formation in cultured COS-7 cells. In the present work, Fchsd2 knockout mice were established to investigate the role of FCHSD2 in hearing. Our data show that stereocilia maintenance is severely affected in cochlear hair cells of Fchsd2 knockout mice, which leads to progressive hearing loss. Moreover, Fchsd2 knockout mice show increased acoustic vulnerability. Noise exposure causes robust stereocilia degeneration as well as enhanced hearing threshold elevation in Fchsd2 knockout mice. Lastly, Fchsd2/Cdc42 double knockout mice show more severe stereocilia deficits and hearing loss, suggesting that FCHSD2 and CDC42 cooperatively regulate stereocilia maintenance.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shandong Province

Publisher

The Company of Biologists

Subject

Cell Biology

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