# Role of SNARE Interactions in Central Synapse Function

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $533,685

## Abstract

Synaptic vesicles are distinct organelles that require multiple integral protein components to be functional.
Despite this complexity, following exocytosis, synaptic vesicles are retrieved, recycled and reused swiftly within
several seconds with high fidelity. The exact mechanisms that underlie this process remain poorly understood.
In this renewal application, we propose to investigate mechanisms underlying synaptic vesicle exocytosis-endocytosis process by visualizing the fusion and retrieval of single synaptic vesicles using fluorescence
imaging methodologies we developed in the last five years. In our hands, this imaging approach has become
rather routine and versatile, amenable to molecular manipulations as well as multimodal imaging at
physiological temperatures with high temporal resolution. Monitoring exo-endocytosis of single synaptic
vesicles enables us to dissect permissive and instructive signals that regulate synaptic vesicle retrieval. Using
this approach, our recent experiments suggested a limited role for the classical endocytosis machinery, while
implying a critical role for the exocytotic fusion machinery, in regulation of quantal single vesicle endocytosis. In
this renewal application, we will fully expand these initial findings and interrogate the mechanisms underlying
single synaptic vesicle retrieval at physiological temperatures with high temporal resolution. To achieve this
goal, we propose three specific aims. In the first aim, we will study the role of dynamins in single synaptic
vesicle retrieval. The second aim will focus on the role of the SNARE (soluble N-ethylmaleimide-sensitive
factor attachment protein receptor) fusion machinery in single synaptic vesicle retrieval. Finally, the third aim
will investigate the roles of endosomal SNAREs in spontaneous synaptic vesicle retrieval. Collectively, these
complementary experiments will elucidate the molecular mechanisms ensuring the fidelity and the time course
of synaptic vesicle retrieval in central synapses. Information attained from these studies will provide new
insight to the synaptic substrates that may be affected by a number of in neuropsychiatric and neurological
disorders including major depressive disorder, autism and schizophrenia.

## Key facts

- **NIH application ID:** 9858429
- **Project number:** 5R01MH066198-18
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Ege T Kavalali
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $533,685
- **Award type:** 5
- **Project period:** 2003-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858429

## Citation

> US National Institutes of Health, RePORTER application 9858429, Role of SNARE Interactions in Central Synapse Function (5R01MH066198-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858429. Licensed CC0.

---

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