ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points.

Autor: Krey JF; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR., Liu C; Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN., Belyantseva IA; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD., Bateschell M; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR., Dumont RA; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR., Goldsmith J; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR., Chatterjee P; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR., Morrill RS; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR., Fedorov LM; Transgenic Mouse Models, University Shared Resources Program, Oregon Health & Science University, Portland, OR., Foster S; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR., Kim J; Department of Otolaryngology-Head & Neck Surgery, Stanford University, Stanford, CA., Nuttall AL; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR., Jones SM; Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, Lincoln, NE., Choi D; OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR., Friedman TB; Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD., Ricci AJ; Department of Otolaryngology-Head & Neck Surgery, Stanford University, Stanford, CA., Zhao B; Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN., Barr-Gillespie PG; Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR.; Vollum Institute, Oregon Health & Science University, Portland, OR.
Jazyk: angličtina
Zdroj: The Journal of cell biology [J Cell Biol] 2022 Apr 04; Vol. 221 (4). Date of Electronic Publication: 2022 Feb 17.
DOI: 10.1083/jcb.202109134
Abstrakt: 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.
(© 2022 Krey et al.)
Databáze: MEDLINE