Essential Role of Sptan1 in Cochlear Hair Cell Morphology and Function Via Focal Adhesion Signaling

Qingxiu Yao,Hui Wang,Zhuangzhuang Li,Feng Liu,Zhipeng Li,Dongzhen Yu,Yumeng Jiang,Yazhi Xing,Hengchao Chen,Jiping Wang,Shankai Yin

doi:10.1007/s12035-021-02551-2

Abstract

Hearing loss is the most common human sensory deficit. Hearing relies on stereocilia, inserted into the cuticular plate of hair cells (HCs), where they play an important role in the perception of sound and its transmission. Although numerous genes have been associated with hearing loss, the function of many hair cell genes has yet to be elucidated. Herein, we focused on nonerythroid spectrin αII (SPTAN1), abundant in the cuticular plate, surrounding the rootlets of stereocilia and along the plasma membrane. Interestingly, mice with HC-specific Sptan1 knockout exhibited rapid deafness, abnormal formation of stereocilia and cuticular plates, and loss of HCs from middle and apical turns of the cochlea during early postnatal stages. Additionally, Sptan1 deficiency led to the decreased spreading of House Ear Institute-Organ of Corti 1 cells, and induced abnormal formation of focal adhesions and integrin signaling in mouse HCs. Altogether, our findings highlight SPTAN1 as a critical molecule for HC stereocilia morphology and auditory function via regulation of focal adhesion signaling.

Highlights

Hearing loss is the most common sensory disorder worldwide with genetic factors contributing to approximately half of congenital hearing loss cases [1]
Together, using a hair cells (HCs)-specific Sptan1 knockout mouse model, we found that Sptan1 is essential for maintaining stereocilia and cuticular plate morphologies
Sptan1-conditional knockout (CKO) mice presented with rapid outer hair cells (OHCs) loss and early-onset deafness

Summary

Introduction

Hearing loss is the most common sensory disorder worldwide with genetic factors contributing to approximately half of congenital hearing loss cases [1]. SPTAN1 is an essential cytoskeletal protein that ensures vital cellular properties, including polarity and cell stabilization. It is involved in cell adhesion, intercellular contact, and apoptosis [19]. Mahendrasingam et al reported that SPTAN1 is present in the cortical lattice of OHCs [11], and Legendre et al reported that SPTAN1 is widely distributed in auditory HCs, supporting cells, and fibroblasts [18].

Methods

Results

Conclusion