# Molecular Analysis of Tmie in sensory hair cells

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $332,563

## Abstract

PROJECT SUMMARY
Transmembrane inner ear-expressed gene (TMIE) encodes a transmembrane protein that essential for hearing
and vestibular function in vertebrates. A recent study of Tmie-/- mice has provided strong evidence for a
central role of TMIE in mechanotransduction in cochlear hair cells. As a member of the transduction complex,
mouse TMIE can bind to a specific isoform of Protocaderin 15 and/or another membrane protein, protein
Lipoma HMGIC Fusion Partner-Like 5 (LHFPL5). Despite these seminal findings, it is not well understood how
TMIE functions as a member of the transduction complex, and to date, its role in vestibular hair cells is
unexplored. The aim of the present proposal is to conduct a comprehensive study of zebrafish Tmie in terms of
identifying the protein motifs that are required for (i) localization of Tmie to stereocilia, (ii) modulation of
mechanotransduction, and (iii) genetic and biochemical interactions with other members of the transduction
complex. The proposed experiments will take advantage of our collection of mechanotransduction mutants and
tools we have developed in zebrafish to investigate the function of Tmie in hair cells. Our preliminary data
indicate that zebrafish Tmie is required the localization of Transmembrane channel like 1 (Tmc1) and Tmc2b to
the stereocilia of hair cells in the inner ear and lateral line organ. This observation is surprising in light of
experiments with Myc tagged TMC2 in mouse outer hair cells, however, the results suggest that TMIE may
play different roles in different cell types. The proposed experiments will expand upon these novel findings and
identify the amino acid motifs in Tmie that promote interaction with Lhfpl5a and the localization of the Tmcs to
the site of mechanotransduction in hair cells. This work will provide mechanistic insights into the role of Tmie in
hair cells and provide a better understanding the molecular determinants of Tmie that are critical for vertebrate
hearing and balance.

## Key facts

- **NIH application ID:** 10000055
- **Project number:** 5R01DC017046-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Teresa A Nicolson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,563
- **Award type:** 5
- **Project period:** 2018-05-04 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000055

## Citation

> US National Institutes of Health, RePORTER application 10000055, Molecular Analysis of Tmie in sensory hair cells (5R01DC017046-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10000055. Licensed CC0.

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