ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points

Jocelyn F. Krey, Chang Liu, Inna A. Belyantseva, Michael Bateschell, Rachel A. Dumont, Jennifer Goldsmith, Paroma Chatterjee, Rachel S. Morrill, Lev M. Fedorov, Sarah Foster, Jinkyung Kim, Alfredl Nuttall, Sherri M. Jones, Dongseok Choi, Thomasb Friedman, Anthony J. Ricci, Bo Zhao, Peter G. Barr-Gillespie

Research output: Contribution to journalArticlepeer-review

Abstract

The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell’s cuticular plate and protecting them from overstimulation. Using superresolution microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed–TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience.

Original languageEnglish (US)
Article numbere202109134
JournalJournal of Cell Biology
Volume221
Issue number4
DOIs
StatePublished - Apr 4 2022

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points'. Together they form a unique fingerprint.

Cite this