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Publication : ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points.

First Author  Krey JF Year  2022
Journal  J Cell Biol Volume  221
Issue  4 PubMed ID  35175278
Mgi Jnum  J:321477 Mgi Id  MGI:6885507
Doi  10.1083/jcb.202109134 Citation  Krey JF, et al. (2022) ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points. J Cell Biol 221(4):e202109134
abstractText  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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