# Molecular Mechanisms of Non-muscle Myosin II Contractility

> **NIH GM R35** · REED COLLEGE · 2026 · $430,383

## Abstract

PROJECT SUMMARY/ABSTRACT
Non-muscle myosin II (NMII) contractility is critical to number cellular processes from development to disease.
NMII is an ATP-dependent molecular motor that functions as a dimer composed of two heavy chains, which are
made of an ATPase/motor domain that binds actin and a coiled-coil tail domain. It is also bound to two
accessory proteins, the essential light chain which plays structural roles, and the regulatory light chain which is
the target of phosphorylation, integrating the molecule into a myriad of signaling pathways. Phosphorylation of
the regulatory light chain leads to a relief of an autoinhibition, opening up the molecule and making it
competent to bind actin, however, by itself it is a poor motor protein. The second required step of activation is
oligomerization into higher ordered, bi-polar filaments. This oligomerization is thought to be regulated by the
tail domain where again, phosphorylation is hypothesized to be the main driver of this transition. While
decades of research have revealed much about these biochemical and biophysical properties, we questioned
whether there were other, yet-to-be revealed, mechanisms that may contribute to NMII’s regulation. The
overarching goal of this proposal is to understand the mechanisms that regulate NMII contractility. In Project 1,
we explore a potential novel NMII binding protein, Split Discs (Spdi). Spdi’s human homolog, SPECC11L has
been implicated in a spectrum of cranial-facial pathologies, highly suggestive of abearent cranial neural crest
cell migration. SPECC1L was initially characterized as actin-microtubule crosslinking proteins, however data
from my lab suggests that its target is NMII and actin. It is our hypothesis that Spdi binds NMII to regulate its
contractility. Through a series of biochemical characterization and cell biology experiments where we elucidate
the mechanism by which Spdi associates with NMII, and employ an ex-vivo developmental model to
understand how its 

## Key facts

- **NIH application ID:** 11331697
- **Project number:** 1R35GM164067-01
- **Recipient organization:** REED COLLEGE
- **Principal Investigator:** Derek Anthony Applewhite
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $430,383
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2031-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11331697

## Citation

> US National Institutes of Health, RePORTER application 11331697, Molecular Mechanisms of Non-muscle Myosin II Contractility (1R35GM164067-01). Retrieved via AI Analytics 2026-07-11 from https://api.ai-analytics.org/grant/nih/11331697. Licensed CC0.

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