# Regulation of hair cell mechanotransduction by PIP2

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Within the stereocilia of hair cells of the inner ear, a variety of molecules including proteins and lipids assemble
into a mechanotransduction (MET) complex. This complex converts mechanical stimuli from sound waves into
electrical signals that can then be propagated through the auditory pathway. Although many protein elements of
the MET complex have been discovered, the lipid elements of this complex are poorly defined. Here, I propose
to elucidate the molecular function of PIP2 in hair cell mechanotransduction. PIP2 has been shown to bind to
TMIE, an essential subunit of the MET complex of cochlear hair cells that binds to TMC1, the likely pore-forming
subunit of the MET channel. In addition, pharmacological depletion of PIP2 in hair cells decreases MET
suggesting that the binding of PIP2 to TMIE affects MET channel function. To test this model and to define the
mechanisms by which PIP2 affects MET in cochlear hair cells, I propose to combine biochemistry and
electrophysiology in order to elucidate how TMIE mutations that perturb PIP2 binding affect MET. I anticipate
that my studies will provide insights into the molecular mechanisms by which a phospholipid that is implicated in
the regulation of the function of many ion channels contributes to the regulation of the mechanotransduction
process in hair cells.

## Key facts

- **NIH application ID:** 11068997
- **Project number:** 1F31DC022480-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jonah Kendahl Mittelstadt
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2025-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11068997

## Citation

> US National Institutes of Health, RePORTER application 11068997, Regulation of hair cell mechanotransduction by PIP2 (1F31DC022480-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/11068997. Licensed CC0.

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