# Regulation of retinal rod transducin

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 2020 · $378,750

## Abstract

ABSTRACT.
Sensory signaling relies on the prototypical pathway mediated by the heterotrimeric G-
proteins, which relays the incoming extracellular signals from the transmembrane G-
protein-coupled receptors (GPCRs) to the enzymes of the second messenger system.
Functional defects in these cascades lead to a variety of neurodegenerative disorders,
which include retinopathies. In addition, GPCRs are among the most important targets of
therapeutic intervention, which account for nearly 50% of drugs on the market. Despite
recent progress in understanding the universal molecular mechanism of G-protein
activation, the biological role of the G-protein beta-gamma subunit complex, and its
exact role during signal transfer from a GPCR to a G-protein remain surprisingly
obscure. Due to the existence of multiple beta and gamma subunit isoforms in a typical
cell and the redundancy of the G-protein-mediated pathways many fundamental
questions of beta-gamma complex biology have been very difficult to address under the
physiological conditions. Thus, major aspects of how this protein complex functions
remain unproven. This proposal builds on our strong groundwork that led to the
discovery that the beta-gamma complex confers the ability of retinal rod photoreceptors
to amplify visual signals and determines the overall sensitivity of these sensory neurons
to light, as well as modulates signal inactivation and light adaptation. Our studies
challenge a rather narrow current view of the beta-gamma complex as an auxiliary
subunit of the G-protein and aim at identifying the biological role of this protein complex,
its exact role during signal transfer from a GPCR to a G-protein, especially during the
key activating step of this reaction – nucleotide exchange on the G-protein alpha
subunit. By using a combination of biochemical, physiological and molecular biophysical
approaches, and by employing several unique mouse lines, we expect to unravel the
contribution of the beta-gamma complex in the underlying mechanisms that are critical to
GPCR signaling and regulation in retinal photoreceptors. As beta-gamma complex has
emerged as a new target of drug design and therapeutic intervention, this proposal will
lead to better understanding of how new therapies may affect GPCR signaling.

## Key facts

- **NIH application ID:** 9915925
- **Project number:** 5R01EY028914-03
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** OLEG G KISSELEV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,750
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915925

## Citation

> US National Institutes of Health, RePORTER application 9915925, Regulation of retinal rod transducin (5R01EY028914-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9915925. Licensed CC0.

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