# Cytoskeletal stability in stereocilia maintenance

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $385,418

## Abstract

PROJECT SUMMARY 
 
Progressive hearing loss is a prevalent health problem that often stems from the loss or dysfunction of sensory 
hair cells in the inner ear.  Hair cell function depends on actin-­based protrusions called stereocilia to detect the 
physical movement of sound.  Functional stereocilia must be maintained for the life of an organism since hair 
cells are not renewed or regenerated.  Thus, stereocilia homeostasis is critical for continued auditory function.  
Tip links transmit force from stereocilia deflection to gate associated mechanotransduction channels found at 
stereocilia tips.  Rows of stereocilia that normally have active channels also have more actin incorporation at 
their tips.  In addition, mutations in the Cdh23 gene, which encodes the tip link component cadherin-­23, 
strongly influence progressive hearing loss and stereocilia length maintenance in mouse models.  Together, 
these data suggest that tip links or mechanotransduction regulates actin dynamics in stereocilia.  Recently, we 
and others found that stereocilia actin cores are highly stable, except at stereocilia tips, where there is more 
dynamic actin turnover.  However, several unanswered questions remain including whether actin binding 
proteins in stereocilia are similarly stable, how the stereocilia actin core is made to be stable and whether actin 
core instability directly influences progressive hearing loss.  It is also unclear how the dynamic region of actin 
at stereocilia tips is regulated and if it contributes to stereocilia length maintenance.  To address these 
questions, we will use transgenic reporters to monitor the dynamics of actin and the actin crosslinker fascin-­2 
in vivo and ex vivo, both in normal mice and in mice with deafness causing mutations in actin binding proteins 
found in stereocilia.  We also hypothesize that stereocilia stability is particularly critical for stereocilia 
maintenance when tip links break.  This model will be tested by measuring actin incorporation as Cdh23 
expression is varied.  If stereocilia shorten following tip link loss, then actin polymerization would be required to 
extend stereocilia back to their original length.  We have found that the actin severing proteins destrin and 
cofilin localize to stereocilia tips, and we will determine if they promote new actin incorporation within the 
dynamic tip zone.  Together, these experiments will provide critical insights into the roles of both extraordinarily 
stable and more dynamic regions of the actin core in maintaining functional stereocilia.

## Key facts

- **NIH application ID:** 10163153
- **Project number:** 5R01DC015495-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** BENJAMIN J PERRIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,418
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163153

## Citation

> US National Institutes of Health, RePORTER application 10163153, Cytoskeletal stability in stereocilia maintenance (5R01DC015495-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163153. Licensed CC0.

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