# The Molecular Basis for Myosin Regulation

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $343,648

## Abstract

Abstract
A critical function for all living organisms is the ability to move when needed. These movements--intracellular
trafficking, cell division, muscle contraction, and cell motility-- are driven by molecular machines that exert an
amazing amount of force considering that they are only a few nanometers across. Given the variety of motor
proteins in the cell, a key question is how motors cooperate and compete while moving cargoes and applying
forces. An emerging paradigm is the notion of specialized motors, or motors that are fine-tuned to perform a
specific function. Despite the importance of these motor proteins, relatively little is known about their individual
adaptations and how these relate to the motility patterns found in the cell. This work focuses on myosin-6 and
myosin-10 and their unique forms of cellular regulation. Myosin-6 plays essential roles in organelle
morphology, cell morphology, cytokinesis, autophagy, and endocytosis, while myosin-10 delivers essential
cargoes such as integrins, cadherins and netrin receptors to filopodia at the leading edge of the cell. Both are
overexpressed in tumors, owing to their roles in membrane trafficking, cell migration, and metastasis. The
work will develop new approaches to control myosin-6 and isolate its activity in cells. One of the main
approaches will be to sequester myosin-6 with light, making cells that have an optically switchable Snell's
waltzer (myosin-6 null) phenotype. Experiments are designed to identify when myosin-6 acts as a passenger,
an anchor, or a transporter in the cells, and if direct handoff from one cargo adaptor to another is required for
function. The proposed work will also investigate how cargo binding and myosin quaternary structure tune
myosin-10's motility. An integrated approach is developed, combining structural studies with functional
reconstitution and single molecule motility assays. This proposal will test the hypotheses that cargo and
extracellular ligand binding are both required for myosin-10 activation, and that cargo can steer myosin-10 from
one type of actin network to another. Completion of this study will yield a comprehensive view of how
cytoskeletal motor proteins are activated and regulated for distinct tasks in the cell. Motor protein regulation is
a process of fundamental biological importance, but is poorly understood. This work will direct future efforts to
understand activation in multiple contexts.

## Key facts

- **NIH application ID:** 9984162
- **Project number:** 5R01GM124272-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Ronald S Rock
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,648
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984162

## Citation

> US National Institutes of Health, RePORTER application 9984162, The Molecular Basis for Myosin Regulation (5R01GM124272-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984162. Licensed CC0.

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