mTORC2 regulates auditory hair cell structure and function

Maurizio Cortada; Soledad Levano; Michael N Hall; Daniel Bodmer

doi:10.1016/j.isci.2023.107687

mTORC2 regulates auditory hair cell structure and function

iScience. 2023 Aug 19;26(9):107687. doi: 10.1016/j.isci.2023.107687. eCollection 2023 Sep 15.

Authors

Maurizio Cortada¹, Soledad Levano¹, Michael N Hall², Daniel Bodmer^{1

3}

Affiliations

¹ Department of Biomedicine, University of Basel, CH-4031 Basel, Switzerland.
² Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
³ Clinic for Otorhinolaryngology, Head and Neck Surgery, University of Basel Hospital, CH-4031 Basel, Switzerland.

Abstract

mTOR broadly controls cell growth, but little is known about the role of mTOR complex 2 (mTORC2) in the inner ear. To investigate the role of mTORC2 in sensory hair cells (HCs), we generated HC-specific Rictor knockout (HC-RicKO) mice. HC-RicKO mice exhibited early-onset, progressive, and profound hearing loss. Increased DPOAE thresholds indicated outer HC dysfunction. HCs are lost, but this occurs after hearing loss. Ultrastructural analysis revealed stunted and absent stereocilia in outer HCs. In inner HCs, the number of synapses was significantly decreased and the remaining synapses displayed a disrupted actin cytoskeleton and disorganized Ca²⁺ channels. Thus, the mTORC2 signaling pathway plays an important role in regulating auditory HC structure and function via regulation of the actin cytoskeleton. These results provide molecular insights on a central regulator of cochlear HCs and thus hearing.

Keywords: Cell biology; Molecular biology.