Repair of noise-induced damage to stereocilia F-actin cores is facilitated by XIRP2 and its novel mechanosensor domain

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 Factin, 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.

Original languageEnglish
Article numbere72681
JournaleLife
Volume12
DOIs
StatePublished - 2023

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