TY - JOUR
T1 - ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points
AU - Krey, Jocelyn F.
AU - Liu, Chang
AU - Belyantseva, Inna A.
AU - Bateschell, Michael
AU - Dumont, Rachel A.
AU - Goldsmith, Jennifer
AU - Chatterjee, Paroma
AU - Morrill, Rachel S.
AU - Fedorov, Lev M.
AU - Foster, Sarah
AU - Kim, Jinkyung
AU - Nuttall, Alfredl
AU - Jones, Sherri M.
AU - Choi, Dongseok
AU - Friedman, Thomasb
AU - Ricci, Anthony J.
AU - Zhao, Bo
AU - Barr-Gillespie, Peter G.
N1 - Funding Information:
We received support from the following core facilities: mass spectrometry from the OHSU Proteomics Shared Resource (partial support from NIH core grants P30 EY010572 and P30 CA069533; Orbitrap Fusion S10 OD012246), mouse production from the OHSU Transgenic Mouse Models core, confocal microscopy from the OHSU Advanced Light Microscopy Core @ The Jungers Center (P30 NS061800 provided support for imaging), and electron microscopy from the OHSU Multi-scale Microscopy Core. PGBG was supported by NIH grants R01DC002368 and R01DC014427. This study was also supported (in part) by the Intramural Research Programs of the NIH, NIDCD DC000039 to T.B. Friedman; B. Zhao was supported by NIH grant R01DC017147, while A.J. Ricci and J. Kim were supported by NIH R01DC0003896. The authors declare no competing interests.
Publisher Copyright:
© 2022 Krey et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
PY - 2022/4/4
Y1 - 2022/4/4
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.202109134
DO - 10.1083/jcb.202109134
M3 - Article
C2 - 35175278
AN - SCOPUS:85124779761
SN - 0021-9525
VL - 221
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
M1 - e202109134
ER -