# Determination of the GIRK channel proteome

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $211,875

## Abstract

Activation of G protein-gated inwardly rectifying potassium (GIRK) channels provides a key inhibitory
signal in the brain that reduces neuronal firing. Many neurotransmitters in the reward pathway, such as
dopamine and GABA, couple to GPCRs that signal through GIRK channels. Prior studies have
established a role for GIRK channels in the response to psychostimulants. A complex network of proteins
is hypothesized to support drug-dependent changes in trafficking and targeting of GIRK channels to
postsynaptic inhibitory synapses, but the identity of these proteins remain largely unknown. To address
this major gap in the field, an innovative technique of proximity-dependent biotin identification (referred to
as iBio-ID) will be used to identify new proteins in the GIRK channel proteome (Aim 1). In this proposal,
GIRK channels will be engineered to biotinylate proteins in vivo (within 50 nanometers of the channel),
and then biotinylated proteins will be purified and identified using tandem mass spectrometry. Preliminary
data show that GIRK channels fused to the biotinylating enzyme are functional, and can biotinylate
proteins in vivo, leading to identification of putative GIRK channel regulators. Following quantitative
analyses, candidate GIRK channel regulator proteins will be assessed for functional interaction with
GIRK channels in neurons. Changes in the GIRK channel proteome with cocaine, using the locomotor
sensitization as a model of addiction, will also be studied (Aim 2). These experiments will provide for the
first time a comprehensive list of proteins in the GIRK channel proteome, and lead to the identity of new
drug-dependent regulators of GIRK channels. Discovery of novel protein targets in the reward pathway
could lead to the development of new treatments for addiction.

## Key facts

- **NIH application ID:** 9970445
- **Project number:** 5R21DA048623-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Paul A Slesinger
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970445

## Citation

> US National Institutes of Health, RePORTER application 9970445, Determination of the GIRK channel proteome (5R21DA048623-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970445. Licensed CC0.

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