# Decoding the functions of myosin II isoforms with super-resolution microscopy

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2021 · $391,816

## Abstract

Decoding the functions of myosin II isoforms with super-resolution microscopy
1) Background and key gaps in our understanding. Cells modify their shape and surroundings to drive
processes vital for eukaryotic life, including cell division, cell migration, and muscle contraction. Forces
generated by the molecular motor, myosin II, drive these processes. Thus, how myosin II assembles filaments
capable of generating force inside of cells is central to our understanding of both developmental processes and
the force-dependent progression of diseases such as cancer. Previous studies have provided elegant details of
how a single filament of myosin II assembles. Steric hindrance limits the number of myosin II molecules that
can be added to a single filament. In order to increase the scale of force generation inside of cells, myosin II
filaments are organized into arrays referred to as “stacks”. While it is well documented that both muscle and
non-muscle isoforms of myosin II are found within stacks, we do not know how stacks assemble. 2) Description
of recent progress by the PI. At the end of his post-doctoral work, the PI showed that super-resolution
microscopy could be used to resolve the structure of a non-muscle myosin IIA (NMIIA) filament and that a
stack of filaments somehow grows from a single filament at the edge of a migrating cancer cell (Burnette et al,
JCB 2014). The first independent paper from the Burnette lab subsequently defined the steps through which a
NMIIA filament physically grows into a stack in a mechanisms we call “expansion”, and that this is regulated by
the motor activity of NMIIA, the density of surrounding actin filaments, and Rho GTPase signaling (Fenix et al,
MBoC 2016). Expansion occurs at the edge of migrating cells during interphase and in the contractile ring
during cell division. The second paper from the Burnette lab showed a force balance between myosin II-based
contractility and adhesion was controlling the shape of the cleavage furrow (Taneja et al, Scientific Reports
2016), similar to how the leading edge of a crawling cell obtains its shape (Burnette et al. JCB 2014). We now
have data suggesting NMIIA and NMIIB play distinct roles during cytokinesis. NMIIA is required for the proper
formation of the contractile ring and initial ingression of the cleavage furrow, and NMIIB is required for the
completion of cytokinesis, as well as maintaining the integrity of the cell cortex throughout mitosis. 3) Overview
of future research program. We propose to continue our research on how myosin II filaments create larger
contractile arrays by addressing three main themes. 1) We will continue to use migrating cells as a model
system to investigate the molecular mechanisms controlling the assembly/disassembly of NMII filament-stacks.
2) We will also explore the different roles of NMIIA and NMIIB during cytokinesis with a particular focus on their
cooperation in creating the contractile arrays in the cleavage furrow and cell cort...

## Key facts

- **NIH application ID:** 10244905
- **Project number:** 5R35GM125028-05
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Dylan Tyler Burnette
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,816
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244905

## Citation

> US National Institutes of Health, RePORTER application 10244905, Decoding the functions of myosin II isoforms with super-resolution microscopy (5R35GM125028-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244905. Licensed CC0.

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