# Exploring the unexpected roles of the sarcomeric myosin family member MYH7b

> **NIH NIH F31** · UNIVERSITY OF COLORADO · 2020 · $37,666

## Abstract

PROJECT SUMMARY
The sarcomeric myosins responsible for muscle contraction are among the most well studied proteins, yet we
are still discovering new roles for this class of molecule. Myosin heavy chain 7b (MYH7b) is a recently
identified gene belonging to the sarcomeric myosin family that appears to have evolved new roles in
mammalian non-muscle tissue. In mammals, MYH7b protein is only expressed in specialized tissues such as
extraocular muscle and muscle spindles and, surprisingly, is found in the inner ear and brain. These
observations are highly unusual as no other muscle myosin has ever been found in non-sarcomeric tissues.
Further, mutations in MYH7b cause hearing loss in humans with no apparent muscle phenotypes, indicating
that MYH7b has an important yet undefined role in non-muscle tissue. Intriguingly, in snakes, MYH7b is found
in the sarcomeres of cardiac and skeletal muscles. Despite these divergent roles in reptiles and mammals,
MYH7b shares high sequence identity between these classes of vertebrates, so it is unclear how mammalian
MYH7b function may deviate in non-muscle tissues from its expected sarcomeric role. The goal of this
proposal is to identify the role and activity of MYH7b in mammalian non-muscle tissue and understand how
mutations in MYH7b contribute to hearing loss. I hypothesize that distinct biophysical and biochemical
properties allow mammalian MYH7b to function in non-muscle environments, and that mutations in MYH7b
disrupt hearing by causing this protein to interfere with normal auditory processes. In Aim 1, I will determine the
physiological role of MYH7b in mammals using mouse models. First, I will investigate the role of MYH7b in wild
type mice by determining subcellular localization, protein interactions, and structures formed by MYH7b in the
inner ear. Next, I will investigate any anatomical and behavioral defects in MYH7b null mice that our lab is
currently maintaining. Finally, I will use CRISPR/Cas gene editing to introduce the human MYH7b mutations
that cause hearing loss into mice and assess hearing function and any resultant anatomical or behavioral
defects. I anticipate this work will reveal how MYH7b functions in the auditory system, which will provide a
foundation for understanding MYH7b function in the mammalian brain. In Aim 2, I will investigate the molecular
function of MYH7b by comparing the biophysical and biochemical activities of recombinant python and human
MYH7b protein. These analyses will address the question of whether these proteins have similar molecular
functions, or whether the mammalian MYH7b activity has diverged from other sarcomeric myosins. I will also
determine the functional impact of the two hearing loss mutations (one in the catalytic motor domain and one in
the structural rod domain of the myosin) on motor properties and the molecule's ability to self assemble into
ordered structures. Collectively, this work will provide a comprehensive understanding of the role of
mammalian...

## Key facts

- **NIH application ID:** 9856878
- **Project number:** 5F31DC017927-02
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Lindsey Anne Lee
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,666
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856878

## Citation

> US National Institutes of Health, RePORTER application 9856878, Exploring the unexpected roles of the sarcomeric myosin family member MYH7b (5F31DC017927-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856878. Licensed CC0.

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