# Role of vesicular TRPM7 channels in synaptic vesicle endocytosis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $343,904

## Abstract

Summary
TRPM7, a Ca2+ permeable nonselective cation channel, is linked to neurodegenerative diseases, and a human
TRPM7 mutation has been identified in Parkinson's diseases (PD), suggesting its critical role in
neurodegeneration. Published work has implied that neuronal death during anoxia and ischemia may be
attributed to Ca2+ overflow via TRPM7. However, roles of TRPM7 in neurons remain undefined at physiological
conditions. Biochemical studies demonstrate that TRPM7 is concentrated on synaptic vesicles and interacts
with vesicular proteins, indicating that TRPM7 may be a critical player in synaptic vesicle recycling. Although
vesicular TRPM7 may provide counterions for release of positively charged acetylcholine during exocytosis in
sympathetic neurons, TRPM7 is also widely distributed in areas with negatively charged glutamate and neutral
GABA as dominant neurotransmitters, suggesting a separate function in these regions. Therefore, the
physiological function of presynaptic TRPM7 in the brain remains largely unknown.
Our preliminary data presented in the research strategy strongly suggest that TRPM7 is the main conduit for
Ca2+ influx in endocytosis, leading us to hypothesize that vesicular TRPM7 serves as the Ca2+ channel for
synaptic vesicle endocytosis. We will test this hypothesis by using a combination of biophysical, live-cell
imaging, and molecular biology techniques.
Our goal is to clearly define, for the first time, the role of TRPM7 in endocytosis. Our studies will have profound
implications for understanding the mechanisms of normal neuronal endocytic processes, how dysfunctions in
these processes lead to neurodegenerative disease, and for development of new therapies to treat diseases
with malfunctions in synaptic vesicle recycling and/or TRPM7.

## Key facts

- **NIH application ID:** 10133166
- **Project number:** 5R01NS110533-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Liang-Wei Gong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $343,904
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133166

## Citation

> US National Institutes of Health, RePORTER application 10133166, Role of vesicular TRPM7 channels in synaptic vesicle endocytosis (5R01NS110533-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133166. Licensed CC0.

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