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ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points.
- Source :
-
The Journal of cell biology [J Cell Biol] 2022 Apr 04; Vol. 221 (4). Date of Electronic Publication: 2022 Feb 17. - Publication Year :
- 2022
-
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.<br /> (© 2022 Krey et al.)
- Subjects :
- Animals
Cell Membrane metabolism
Cytoplasm metabolism
HEK293 Cells
Hair Cells, Auditory metabolism
Hair Cells, Auditory pathology
HeLa Cells
Hearing Loss pathology
Humans
Mice, Inbred C57BL
Mice, Knockout
Nuclear Proteins chemistry
Protein Aggregates
Protein Binding
Protein Domains
Stereocilia ultrastructure
Mice
Microfilament Proteins metabolism
Nuclear Proteins metabolism
Stereocilia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 221
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 35175278
- Full Text :
- https://doi.org/10.1083/jcb.202109134