# Mechanisms of Vesicle Fusion and Transmitter Release

> **NIH NIH R01** · CORNELL UNIVERSITY · 2020 · $322,000

## Abstract

Summary
Membrane fusion is a key process in cell biology from intracellular transport to release of
neurotransmitters and hormones and viral infection. This release occurs from the interior of
the secretory vesicle to the outside of the cell via formation of a fusion pore. In
neurosecretory cells release is stimulated by calcium entry, which induces rapid release of
primed vesicles that form a readily releasable pool. The SNARE (Soluble NSF Attachment
REceptor) complex, which in mammalian neurons and neuroendocrine cells is composed of
the proteins synaptobrevin-2, syntaxin-1, and SNAP-25, plays a key role in vesicle fusion.
One example for the medical relevance of SNARE complex function is the BoTox treatment,
which inhibits transmitter release by specific cleavage of the SNARE protein SNAP-25.
Although the components of the SNARE complex and the identity of several accessory
proteins are known, it is still unclear how SNARE complex assembly induces priming of
vesicles, fusion pore opening and dilation, and how many SNARE complexes participate in
these steps. One method to probe conformational changes in a protein complex utilizes
Fluorescence Resonance Energy Transfer (FRET). In this approach, a FRET donor and a
FRET acceptor are incorporated into the protein. The fluorescent proteins CFP and YFP (and
their derivatives with similar spectra) form a suitable FRET pair and have been incorporated
at the N terminal ends of the SNAP-25 SNARE domains. We recently found that this SNARE
COmplex REporter (SCORE) shows a rapid transient FRET change specifically associated
with fusion events. This research uses FRET probes of SNAP-25 as well as syntaxin-1 based
FRET constructs that report transitions between the open and closed state of syntaxin to
elucidate the nanomechanical molecular steps and rearrangements associated with vesicle
priming and fusion.

## Key facts

- **NIH application ID:** 9843170
- **Project number:** 5R01GM121787-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Manfred LINDAU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $322,000
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843170

## Citation

> US National Institutes of Health, RePORTER application 9843170, Mechanisms of Vesicle Fusion and Transmitter Release (5R01GM121787-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843170. Licensed CC0.

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