# Structural Basis of Quantal Release

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $121,230

## Abstract

PROJECT SUMMARY/ABSTRACT
Vesicular glutamate transporters (VGLUTs) package the major excitatory neurotransmitter glutamate into
synaptic vesicles, thus play a critical role in quantal release and neurotransmission. Despite decades of
research, the mechanism of glutamate transport by the VGLUTs and its regulation under different ionic and pH
conditions during exocytosis and endocytosis remains poorly understood. The lack of molecular level
understanding of the structure and function of VGLUTs severely hinders our ability to understand their role in
normal brain function, as well as in many psychiatric and neurological conditions where malfunction of VGLUTs
has been implicated. This proposal aims to bridge this gap by providing a molecular blue print of a mammalian
VGLUT protein with atomic details. Specifically, the candidate Dr. Fei Li will determine high-resolution
structures of the rat VGLUT1 (rVGLUT1) by cryo electronmicrosocpy (cryo-EM) (Aim 1, mentored) and
characterize its function by electrophysiology (Aim 2, mentored). Dr. Fei Li will further determine the
structure of the native synaptic vesicle by cryo electrontomography (cryo-ET) (Aim 3A, mentored) and
to reveal the higher order organization and interactions of synaptic vesicle membrane proteins (Aim
3B, independent). The goal of this K99/R00 Pathway to Independence Award proposal is to enhance Dr. Li’s
knowledge in neuroscience and to provide opportunity of additional training in several key techniques that are
critical to launching her independent research career focusing on the structure and function of neuronal
membrane proteins in a leading research institution. The proposed aims allow Dr. Li to explore new biological
questions that she can continue to investigate in her independent career while providing opportunities for
training at the same time. Dr. Li has a strong interest in membrane protein structure and function in the context
of brain physiology, and a strong background in membrane protein and X-ray crystallography. To guide the
proposed project and to enhance her career prospects, Dr. Li has selected three leading scientists in,
respectively, membrane proteins (Dr. Robert Stroud), electron microscopy (Dr. Yifan Cheng), as well as
electrophysiology and neuroscience (Dr. Robert Edwards) as her co-mentors. Training through this project will
allow Dr. Li to build a highly versatile and integrative skill set extending her background in membrane proteins
and X-ray crystallography to the state-of-the-art cryo-EM and cryo-ET technology. Skills in electrophysiology
will provide her with the tools required for functional analysis. Together, the research project and training
program proposed in this award will play a critical role in preparing Dr. Li for a successful independent
research career.

## Key facts

- **NIH application ID:** 9900872
- **Project number:** 5K99MH119591-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Fei Li
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $121,230
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900872

## Citation

> US National Institutes of Health, RePORTER application 9900872, Structural Basis of Quantal Release (5K99MH119591-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9900872. Licensed CC0.

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