# Regulation of hair cell functions

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2020 · $408,734

## Abstract

Prestin, a motor protein serves as the cochlear amplifier contributing towards the sensitivity of the
mammalian inner ear. Moreover, prestin expressed in heterologous systems yields functional characteristics
that are not consistent with the bona-fide OHC properties, raising the possibility that there are missing prestin-
interacting proteins that should be identified to understand the mechanisms of this remarkable motor protein.
Using innovative genetic, molecular, cellular, and functional imaging strategies, we have invoke this
hypothesis. In contrast to the dogma that prestin is uniquely OHC-specific, we hypothesize that the authentic
cochlear amplifier consists of prestin and its family member, SLC26A6. We further hypothesize that SLC26A6
is required as an efficient transporter to create intracellular Cl- microdomain for the proper function of prestin.
 To test the hypothesis, we propose the following three aims: 1) To test the spatial expression and co-
localization of prestin and slc26a6 in OHCs. First, we will determine the expression and co-localization of
prestin and slc26a6 in OHCs using quantitative real-time PCR (qRT-PCR), immunofluorescence confocal
microscopy and immuno-electron microscopy (immuno-EM). Prestin-/- and slc26a6-/- mice will serve as
negative controls. 2) To test for the physical interaction or the hetero-oligomerization of prestin and slc26a6. To
directly test for possible physical interaction or co-assembly between prestin and SLC26A6, we will use co-
immunoprecipitation (co-IP) and fluorescence resonance energy transfer (FRET) techniques. 3) To determine
the in vitro and in vivo functional roles of the interaction or hetero-oligomerization of prestin and slc26a6. We
will record the anion exchange activities and the nonlinear capacitance of the co-expressed prestin and
slc26a6. We will design prestin-slc26a6 chimera constructs to further test for function interaction of the two
proteins. Finally, we will test the prediction that in the absence of slc26a6, the motor functions of prestin will be
severely altered, compromising the hearing sensitivity of slc26a6 null mutant mice.
 These studies will reveal a missing functional component of the cochlear amplifier and may divulge a
new therapeutic target for the treatment of hearing loss or deafness. The outcomes of these studies will alter
our present understanding of the functional mechanisms of prestin in OHCs, and would shift the paradigm from
“prestin-centric” towards orchestral proteins that operate to amplify sound in the inner ear.

## Key facts

- **NIH application ID:** 9897410
- **Project number:** 5R01DC015252-04
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** EBENEZER N YAMOAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,734
- **Award type:** 5
- **Project period:** 2017-04-05 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897410

## Citation

> US National Institutes of Health, RePORTER application 9897410, Regulation of hair cell functions (5R01DC015252-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897410. Licensed CC0.

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