# Leveraging the genetics and biochemistry of UNC-13 to uncover mechanisms driving neurotransmitter secretion

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $43,655

## Abstract

PROJECT SUMMARY
Communication between cells in the brain occurs predominantly via chemical secretion in neuronal
specializations called presynaptic terminals where synaptic vesicles (SVs) fuse with the plasma membrane to
release neurotransmitter molecules. These membrane fusion events are tightly controlled and modulated by key
synaptic proteins such as the neuronal SNARE proteins as well as Munc13-1/UNC-13, Munc18-1/UNC-18,
Complexin, and Synaptotagmin. Munc13-1 is major hub for every step in synaptic transmission. Moreover,
mutations in the human UNC-13 ortholog are associated with severe neurological and developmental disorders.
Importantly, the mechanisms underlying the various Munc13-1 functions are largely unknown. We recently
characterized a novel domain at the C-terminus of Munc13-1 termed HC2M that plays a role in SV
docking/priming, and mutations in this domain have a devastating impact on synaptic transmission and nervous
system function in the model organism C. elegans. Using a combination of genetic, behavioral, imaging, and
biochemical methods, we will investigate the role of UNC-13 in driving the assembly of the neuronal SNAREs, a
critical first step in SV priming. This project will shed light on some of the enduring mechanistic mysteries
underlying synaptic transmission.

## Key facts

- **NIH application ID:** 10911831
- **Project number:** 5F31NS130894-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Ziasmin Shahanoor
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,655
- **Award type:** 5
- **Project period:** 2023-08-17 → 2025-06-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911831

## Citation

> US National Institutes of Health, RePORTER application 10911831, Leveraging the genetics and biochemistry of UNC-13 to uncover mechanisms driving neurotransmitter secretion (5F31NS130894-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10911831. Licensed CC0.

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