# VASP ubiquitination regulates actin dynamics in dendritic spines

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $36,960

## Abstract

ABSTRACT
Filopodia are dynamic, actin-rich structures that extend outward from the cell and explore the local environment.
In neurons, filopodia are critical for numerous stages of development, including neuritogenesis, axon guidance,
and dendritic spine formation. Defects in any of these stages of neuronal development can result in improper
synaptic connectivity, neurodevelopmental disorders, and psychiatric syndromes. The Ena/VASP of actin
polymerizes is well appreciated to localize to the filopodial tip complex and influence actin dynamics. Recently,
the Gupton lab showed VASP transiently co-localizes with the E3 ubiquitin ligase TRIM9 at the filopodial tip.
TRIM9 was required for the reversible, non-degradative ubiquitination of VASP and this modification was
associated with decreases in filopodia stability and number. Appropriate control of filopodial dynamics is critical
for several neuronal processes, yet we still do not understand how VASP is regulated at the filopodial tip. My
central hypothesis that VASP-Ub negatively regulates actin dynamics in filopodia and dendritic spines. To test
this hypothesis, I will chemically ubiquitinate and fluorescently label purified VASP protein. Using various
biochemical assays, I will define the impact of ubiquitination on VASP tetramerization and VASP-mediated
regulation of actin dynamics. Mechanistically understanding the impact of VASP ubiquitination in vitro is critical
in understanding the cellular role of ubiquitinated VASP (VASP-Ub). Furthermore, I will examine the localization
and function of VASP-Ub in dendritic spines. Previous work has shown that VASP is required for proper dendritic
spine formation and my preliminary data shows that VASP-Ub localizes to the post-synaptic density. I will
examine VASP and VASP-Ub abundance and localization during dendritic spine maturation and chemically
induced plasticity will be analyzed in forebrains and cultured cortical and hippocampal neurons isolated from
wild-type and Trim9-/- mice using both microscopy-based and biochemical assays. These experiments will
determine how ubiquitination regulates VASP activity, and consequently actin polymerization and synaptic
plasticity, in dendritic spines. Appropriate control of the cytoskeleton is critical for dendritic spine formation, and
synaptic transmission, yet it is still unknown how actin dynamics are controlled in these specialized neuronal
structures. Working at the interface of biochemistry, cell biology, and neuroscience, I will determine how non-
degradative ubiquitination regulates the actin polymerase VASP and shapes neuronal morphology and function.

## Key facts

- **NIH application ID:** 10049192
- **Project number:** 5F31NS113381-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Laura E McCormick
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,960
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049192

## Citation

> US National Institutes of Health, RePORTER application 10049192, VASP ubiquitination regulates actin dynamics in dendritic spines (5F31NS113381-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10049192. Licensed CC0.

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