Repair of Noise-Induced Damage to Stereocilia F-Actin Cores Is Facilitated by XIRP2 and Its Novel Mechanosensor Domain

Authors

Elizabeth L Wagner
Jun-Sub Im
Stefano Sala
Maura I Nakahata
Terence E Imbery
Sihan Li
Daniel Chen
Katherine Nimchuk
Yael Noy
David W Archer
Wenhao Xu
George Hashisaki
Karen B Avraham
Patrick W Oakes
Jung-Bum Shin

Publication Date

6-9-2023

Journal

eLife

Abstract

Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as 'gaps' in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein, we show that gaps in mouse auditory hair cells are largely repaired within 1 week of traumatic noise exposure through the incorporation of newly synthesized actin. We provide evidence that Xin actin binding repeat containing 2 (XIRP2) is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps. Recruitment of XIRP2 to stereocilia gaps and stress fiber strain sites in fibroblasts is force-dependent, mediated by a novel mechanosensor domain located in the C-terminus of XIRP2. Our study describes a novel process by which hair cells can recover from sublethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.

Keywords

actin, cell biology, hair cells, hearing loss, mechanosensation, mouse, neuroscience, repair, stereocilia

Comments

Supplementary Materials

PMID: 37294664