# Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $30,433

## Abstract

PROGRAM DESCRIPTION
The overarching research goal of my lab is to define cellular and molecular mechanisms mediating cellular shape
change. Cellular shape change is a fundamental characteristic of metazoan cells, key to development,
physiology, and pathology. The formation and plasticity of neural networks are key examples of cell shape
change during development and physiology, whereas cell shape and motility goes awry in pathological
conditions, such as melanoma. We study two main themes during cellular shape change: The active control of
the cytoskeleton, which is acknowledged as critical to cellular shape change, and the concurrent remodeling of
the plasma membrane, which is perhaps less well appreciated. Although many cytoskeletal and membrane
remodeling components are known and their biochemical and structural characteristics described, we lack a
systematic understanding of how these disparate systems are regulated and coordinated to orchestrate cellular
shape change. Perhaps the most important problem in cell morphogenesis is understanding how cells perceive
cues in their environment and convert this extracellular information into shape changes through coordinated
cytoskeletal dynamics and plasma membrane remodeling; this is the focus of this proposal. Functions of small
GTPases and kinases have been extensively studied in regulating cytoskeletal dynamics and membrane
remodeling. Work from my lab identified an emerging role for E3 ubiquitin ligases in regulated cellular shape
change. We identified two E3 ubiquitin ligases, TRIM9 and TRIM67, which regulate cytoskeletal and exocytic
proteins and cellular shape changes in response to netrin. The extracellular morphogen netrin promotes neuronal
morphogenesis and cancer progression. Despite these important consequences, we know little about how cells
interpret netrin into shape changes. TRIM9 and TRIM67 provide an excellent opportunity to investigate the
function of ubiquitination in cytoskeletal and membrane remodeling, and how these functions are coordinated
during netrin triggered cell shape change and motility. TRIM9 and TRIM67 share similar sequences, localization,
and interaction partners, however our studies identified distinct functions of these related proteins and
antagonistic phenotypes associated with their deletion. The overarching goal of this program is to test the
hypothesis that TRIM9 and TRIM67 coordinate cytoskeletal dynamics and exocytosis during netrin-dependent
morphogenesis in multiple cell types. Since netrin plays roles in both neuronal development and cancer
pathogenesis, our work will exploit developing neurons and migrating melanoma cells as model systems. Our
preliminary and published data indicate both cell types respond to netrin and express TRIM9 and TRIM67. Our
work will illuminate fundamental generalities and cell type specific mechanisms of shape change, providing
mechanistic understanding of the coordination of the cytoskeleton and membrane trafficking during ...

## Key facts

- **NIH application ID:** 10833896
- **Project number:** 3R35GM135160-05S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Stephanie Gupton
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $30,433
- **Award type:** 3
- **Project period:** 2019-12-01 → 2025-01-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833896

## Citation

> US National Institutes of Health, RePORTER application 10833896, Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change (3R35GM135160-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10833896. Licensed CC0.

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