# Mechanisms and regulation of extracellular vesicle traffic in the nervous system

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 2020 · $353,853

## Abstract

The goal of this project is to understand the molecular mechanisms of extracellular vesicle (EV) trafficking in
the nervous system in vivo. EVs are small vesicles secreted from donor cells that can carry a diverse array of
cargoes, and have recently come to the forefront as a novel mode of intercellular traffic and communication in
the brain. EVs are thought to contribute to many human health conditions, including the spread of pathological
proteins in neurodegenerative disease. However, because most studies of EVs are conducted with cells in
culture, little is known about the release, uptake and fate of EVs in the diverse interacting cell types of the
intact nervous system. We have developed a system in which to study traffic of endogenous neuronal EV
cargoes in a living animal, using cutting edge genetic and cell biological tools available in Drosophila. Using
this system, we discovered an unexpected role for synaptic periactive zone (PAZ) membrane remodeling
machinery in EV cargo sorting, stability and release from axon terminals at the Drosophila larval
neuromuscular junction. We also found that endogenous EV cargo release is dynamically regulated by
neuronal activity. Finally, we made the surprising discovery that released EVs are partially protected from the
target cell cytoplasm, suggesting the possibility that additional regulatory steps may govern their exposure
and/or degradation upon internalization to recipient cells. Our proposed research will elucidate how cellular
membrane traffic machinery controls the release, uptake, and fate of EV cargoes. To achieve these goals we
will use advanced Drosophila genetics, live cell imaging techniques, structured illumination microscopy,
electron microscopy, and tissue-specific detection and manipulation of EV cargoes in donor and recipient cells.
Specifically, we propose: 1) To elucidate in vivo mechanisms of EV traffic and release by PAZ proteins. 2) to
determine how activity regulates neuronal traffic of endogenous EV cargoes and 3) to determine the fate of
NMJ EV cargoes, at rest and in response to neuronal activity. Given the conserved nature of synaptic
membrane trafficking machinery, our findings and tools will lay the foundation for new insights into endogenous
EV traffic in many aspects of nervous system function, including in human neurological disease.

## Key facts

- **NIH application ID:** 9829596
- **Project number:** 5R01NS103967-03
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** Avital Adah Rodal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,853
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829596

## Citation

> US National Institutes of Health, RePORTER application 9829596, Mechanisms and regulation of extracellular vesicle traffic in the nervous system (5R01NS103967-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9829596. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*