# Mechanisms of GPCR-induced Autophagy

> **NIH NIH P20** · UNIVERSITY OF MAINE ORONO · 2024 · $270,079

## Abstract

G-protein coupled receptors (GPCRs) commonly detect extracellular signals to control cellular
responses. In many cases, GPCRs detect stresses that lead to activation of the cellular
recycling process called autophagy. In the yeast mating pathway, GPCRs are used to detect
and grow towards potential mating partners. The mating pathway initiates autophagy, despite
the lack of an external stress. We hypothesize that GPCR activation of autophagy represents a
novel negative feedback loop that reduces GPCR signaling through enhanced degradation of
the receptor. In Aim1 we will test the hypothesis that pheromone signaling drives selective
autophagy rather than bulk autophagy through a combination of Gα activation of PI3 Kinase and
other pheromone specific signals. In Aim 2 we will test the hypothesis that pheromone induced
autophagy serves as a negative feedback loop to enhance receptor desensitization. These
studies will provide a molecular understanding of the interplay between GPCR signaling and
autophagy, two systems that are well conserved between yeast and humans and in which yeast
research has a long history of providing meaningful advances in the understanding of human
biology. The understanding of GPCR and autophagy interactions is important to understanding
the potential combinatorial effects of the myriad GPCR and autophagy targeting drugs currently
used to treat human disease.

## Key facts

- **NIH application ID:** 10821307
- **Project number:** 5P20GM144265-02
- **Recipient organization:** UNIVERSITY OF MAINE ORONO
- **Principal Investigator:** Joshua Brian Kelley
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $270,079
- **Award type:** 5
- **Project period:** 2023-04-05 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821307

## Citation

> US National Institutes of Health, RePORTER application 10821307, Mechanisms of GPCR-induced Autophagy (5P20GM144265-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10821307. Licensed CC0.

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