# Supplement for Mechanotransduction-Dependent Remodeling of the Stereocilia Cytoskeleton

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2020 · $74,072

## Abstract

PROJECT SUMMARY/ABSTRACT
 Stereocilia are the sensory machinery of the inner ear sensory hair cells. We found that the stability of
these actin-filled projections depends on the constant influx of calcium through the mechano-electrical
transduction (MET) channels that are located at the tips of stereocilia (Velez-Ortega, et al., eLife, 2017).
We found that the blockage of MET channels or the breakage of their gating tip links leads to the
shortening of stereocilia; but once the blockage is removed or the tip links regenerate, stereocilia are
able to regrow. Based on the changes in stereocilia height in response to variations in the resting MET
current, I hypothesized that the stereocilia actin cytoskeleton exhibits activity-dependent plasticity.
 Aim 2 of the parent grant (R21 DC017247) has been studying the contribution of myosin XV isoforms
in the MET-dependent regulation of stereocilia height using several myosin XV mutant mice. Our results
thus far indicate that the two types of mammalian auditory hair cells (inner vs. outer hair cells) have
different molecular mechanisms driving the MET-dependent changes in the stereocilia cytoskeleton. In
addition, we have observed interesting MET-dependent changes to the resting tilt of the hair bundle that
could arise from changes at the level of the stereocilia rootlets and/or the cuticular plate.
 The goal of this Administrative Supplement is to obtain resources (for personnel and supplies) that
would allow us to perform focused ion beam scanning electron microscopy (FIB-SEM) imaging to (i)
answer some questions that traditional SEM imaging has not been able to address due to the difficulty in
obtaining accurate 3D measurements of the extremely short stereocilia in some myosin XV mutants; and,
using the same FIB-SEM data sets, to (ii) further explore the mechanotransduction-dependent
rearrangements of the stereocilia rootlets and/or cuticular plate. In addition, this supplement would allow
Dr. Velez-Ortega to spend less time on the bench performing experiments and, instead, more time on
data analysis and manuscript preparation. This `shift' in the focus of Dr. Velez-Ortega's effort would
minimize a decrease in the progress of the parent grant due to the upcoming birth of her child in the Fall
of 2020.

## Key facts

- **NIH application ID:** 10170923
- **Project number:** 3R21DC017247-03S1
- **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:** $74,072
- **Award type:** 3
- **Project period:** 2018-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170923

## Citation

> US National Institutes of Health, RePORTER application 10170923, Supplement for Mechanotransduction-Dependent Remodeling of the Stereocilia Cytoskeleton (3R21DC017247-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10170923. Licensed CC0.

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