# Proteomic analysis of the electrical synapse

> **NIH NIH R21** · UNIVERSITY OF OREGON · 2020 · $405,625

## Abstract

The nervous system uses two forms of fast synaptic transmission, chemical and electrical, that both contribute
to the dynamic computations that create thought, feelings, and actions. Chemical synapses are well studied,
and the biochemical mechanisms by which neurotransmitter is released and received are well understood. By
contrast, we know relatively little about the macromolecular complex of the electrical synapse. Electrical
synapses are made from tens to thousands of gap junction channels that create direct, low-resistance routes of
cytoplasmic communication between neurons. They contributed to sophisticated function in neural circuit
computation, they display plasticity through a number of short- and long-term mechanisms, and their assembly
is regulated during development. Together, this all suggest a complex macromolecular structure that controls
their formation and function, yet a critical barrier to progress in the field remains in the identification of the
proteins of the electrical synapse. The overarching goal of the proposal is to establish zebrafish electrical
synapses as a model to understand their proteomic diversity. Aim1 will demonstrate that electrical synapse
proteins can be identified using genome engineered zebrafish that express electrical synapse proteins tagged
with TurboID. TurboID is an evolved E.coli protein that allows for in vivo, proximity-depending labeling of
proteins with biotin. Such biotinylated proteins can then be efficiently isolated from the animal and analyzed
using mass spectrometry. Aim2 will then assess the biochemical interactions and cellular localization of the
identified proteins using expression systems for protein-protein interactions and in vivo immunohistochemistry
in zebrafish. If successful, this grant will fundamentally shift the understanding of electrical synapses, revealing
proteins involved in trafficking pathways, synaptic structure, and functional regulation. The proposed studies
will provide novel insight into the molecular complexes of the electrical synapse in a model vertebrate,
providing a foundation for the identification of targets for therapy of neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10042722
- **Project number:** 1R21NS117967-01
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Adam C Miller
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,625
- **Award type:** 1
- **Project period:** 2020-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042722

## Citation

> US National Institutes of Health, RePORTER application 10042722, Proteomic analysis of the electrical synapse (1R21NS117967-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10042722. Licensed CC0.

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