# Mechanisms of Hair Cell Mechanotransduction Channel Gating

> **NIH NIH R21** · HARVARD MEDICAL SCHOOL · 2021 · $169,500

## Abstract

Project Summary
Auditory mechanotransduction channels reside at the tips of hair-cell stereocilia, where they mediate the
conversion of sound-induced mechanical stimuli into electrical signals that are transmitted to the brain. These
channels open in response to mechanical force and allow a selective influx of cations into hair cells. During
gating, a channel component is thought to undergo a particularly large conformational change - with an
estimated gating movement of ~ 4 nm. Their molecular identity has been pursued for over two decades. Recently,
we provided strong evidence that TMC1 forms the pore of the auditory transduction channels and bears
structural similarity to the TMEM16 family of ion channels. But we still don’t know how the channel works at a
molecular level. This is a fundamental aspect of hearing, as it underlies the conversion of sound into neural
signals by the mechanotransduction complex. The proposed research will integrate protein biochemistry,
molecular engineering, and hair cell physiology to probe the gating domains of TMC1. It will pave a path to
more extensive studies combining structural and functional biochemistry with single-cell physiology to provide
a comprehensive molecular characterization of how mechanotransduction channels open in response to force.

## Key facts

- **NIH application ID:** 10127619
- **Project number:** 5R21DC018631-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Nurunisa Akyuz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,500
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127619

## Citation

> US National Institutes of Health, RePORTER application 10127619, Mechanisms of Hair Cell Mechanotransduction Channel Gating (5R21DC018631-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10127619. Licensed CC0.

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