# Mechanotransduction-Dependent Remodeling of the Stereocilia Cytoskeleton

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2020 · $153,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Mechanosensitivity of the inner ear hair cells depends on actin-filled cellular projections known as
stereocilia. We recently found that the stability of the stereocilia cytoskeleton depends on the constant
influx of calcium ions through the mechano-electrical transduction (MET) channels that are located at
the tips of stereocilia (Velez-Ortega, et al., eLife 2017). We showed that the blockage of MET channels
or the breakage of the tip links that gate these channels leads to the selective shortening of transducing
stereocilia in the bundle (i.e. only the middle and short row stereocilia harbor MET channels). Once the
MET blockage is removed or the tip links regenerate, the shortened stereocilia regrow. An increase in
intracellular calcium buffering also led to the selective remodeling of transducing stereocilia, indicating
that calcium ions are the main component of the MET current regulating the stereocilia morphology.
Stereocilia remodeling in response to variations in the resting MET current represents an activity-
dependent plasticity of the stereocilia actin cytoskeleton, which may initiate profound changes in the
hair bundle morphology in various types of hereditary or acquired hearing losses. Therefore, this project
begins the search for the molecular players involved in the MET-dependent remodeling of the
stereocilia cytoskeleton. Aim 1 will determine the MET-dependent changes in the actin incorporation
into the stereocilia, potential actin treadmill, and actin isoform composition. Given that myosin XV
delivers the elongation machinery to the tips of stereocilia, Aim 2 will test for the contribution of myosin
XV isoforms in the MET-dependent regulation of the stereocilia height. This study is significant,
because it may uncover the molecular mechanisms of the fine adjustments of the staircase architecture
of the hair cell bundles. Moreover, stereocilia shortening—and perhaps eventual stereocilia
disappearance—could occur after noise exposure (when the MET current is reduced due to tip link
breakage) or in certain cases of congenital deafness (due to impaired MET current). Therefore, this
study will expand our knowledge of the molecular mechanisms of various types of hearing loss.

## Key facts

- **NIH application ID:** 9959391
- **Project number:** 5R21DC017247-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Alejandra Catalina Velez Ortega
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959391

## Citation

> US National Institutes of Health, RePORTER application 9959391, Mechanotransduction-Dependent Remodeling of the Stereocilia Cytoskeleton (5R21DC017247-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9959391. Licensed CC0.

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