Annexin A4 Is Dispensable for Hair Cell Development and Function.

Nana Li,Zhigang Xu,Haibo Du,Yuehui Xi,Hao Zhou

doi:10.3389/fcell.2021.680155

Nana Li, Zhigang Xu + Show 3 more

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https://doi.org/10.3389/fcell.2021.680155

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Abstract

Annexin A4 (ANXA4) is a Ca2+-dependent phospholipid-binding protein that is specifically expressed in the cochlear and vestibular hair cells, but its function in the hair cells remains unknown. In the present study, we show that besides localizing on the plasma membrane, ANXA4 immunoreactivity is also localized at the tips of stereocilia in the hair cells. In order to investigate the role of ANXA4 in the hair cells, we established Anxa4 knockout mice using CRISPR/Cas9 technique. Unexpectedly, the development of both cochlear and vestibular hair cells is normal in Anxa4 knockout mice. Moreover, stereocilia morphology of Anxa4 knockout mice is normal, so is the mechano-electrical transduction (MET) function. Consistently, the auditory and vestibular functions are normal in the knockout mice. In conclusion, we show here that ANXA4 is dispensable for the development and function of hair cells, which might result from functional redundancy between ANXA4 and other annexin(s) in the hair cells.

Highlights

Hair cells are mechanosensitive sensory receptor cells in the cochlea and vestibular organs, characterized by their hairy-looking, actin-based stereocilia on the apical surface
Annexin A4 (ANXA4) Is Localized at the Stereociliary Tips and Plasma Membrane of Cochlear Hair Cells
Identification of ANXA4/5-binding partners in the stereocilia as well as examination of the stereocilia phenotypes of Anax4/Anxa5 double knockout mice will help us to learn more about their roles in the stereocilia

Summary

Introduction

Hair cells are mechanosensitive sensory receptor cells in the cochlea and vestibular organs, characterized by their hairy-looking, actin-based stereocilia on the apical surface. Transcriptomic and proteomic analysis have identified several proteins that are essential for hair cell development and/or function (Richardson et al, 2011; Cai et al, 2015; Scheffer et al, 2015; Krey et al, 2018). Several ATOH1-regulated genes have been identified through transcriptomic analysis, such as Anxa, Rbm, Srrm, et al (Cai et al, 2015). We and others showed that RBM24 and SRRM4 are important for hair cell development and/or function through regulating mRNA splicing or stability (Nakano et al, 2012; Zhang et al, 2020; Zheng et al, 2020)

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