# Administrative Equipment Supplement for GM135160

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $90,000

## Abstract

PROJECT SUMMARY
Cellular shape change is a fundamental characteristic of metazoan cells that is 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 cancers such as
melanoma. The active control of the cytoskeleton is acknowledged as critical to cellular shape change,
whereas the concurrent remodeling of the plasma membrane 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.
Functions of small GTPases and kinases are well 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. Netrin is an extracellular morphogen that promotes
neuronal morphogenesis and the progression of cancers, such as melanoma. TRIM9 and TRIM67 thus
provided an excellent entry point for the lab to investigate how cytoskeletal and membrane remodeling are
coordinated during netrin triggered morphogenesis 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 neurons and migrating melanoma cells. Our work will provide fundamental mechanistic
understanding of the regulation of the cytoskeleton and membrane trafficking during development and
metastasis.

## Key facts

- **NIH application ID:** 10387434
- **Project number:** 3R35GM135160-02S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Stephanie Gupton
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $90,000
- **Award type:** 3
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387434

## Citation

> US National Institutes of Health, RePORTER application 10387434, Administrative Equipment Supplement for GM135160 (3R35GM135160-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387434. Licensed CC0.

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