The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.

Gustatory Receptor 64 (Gr64) genes are a cluster of 6 neuronally expressed receptors involved in sweet taste sensation in Drosophila melanogaster. Gr64s modulate calcium signalling and excitatory responses to several different sugars. Here, we discover an unexpected nonneuronal function of Gr64 rece...

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Main Authors: Michael E Baumgartner, Alex Mastrogiannopoulos, Iwo Kucinski, Paul F Langton, Eugenia Piddini
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-07-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001710&type=printable
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author Michael E Baumgartner
Alex Mastrogiannopoulos
Iwo Kucinski
Paul F Langton
Eugenia Piddini
author_facet Michael E Baumgartner
Alex Mastrogiannopoulos
Iwo Kucinski
Paul F Langton
Eugenia Piddini
author_sort Michael E Baumgartner
collection DOAJ
description Gustatory Receptor 64 (Gr64) genes are a cluster of 6 neuronally expressed receptors involved in sweet taste sensation in Drosophila melanogaster. Gr64s modulate calcium signalling and excitatory responses to several different sugars. Here, we discover an unexpected nonneuronal function of Gr64 receptors and show that they promote proteostasis in epithelial cells affected by proteotoxic stress. Using heterozygous mutations in ribosome proteins (Rp), which have recently been shown to induce proteotoxic stress and protein aggregates in cells, we show that Rp/+ cells in Drosophila imaginal discs up-regulate expression of the entire Gr64 cluster and depend on these receptors for survival. We further show that loss of Gr64 in Rp/+ cells exacerbates stress pathway activation and proteotoxic stress by negatively affecting autophagy and proteasome function. This work identifies a noncanonical role in proteostasis maintenance for a family of gustatory receptors known for their function in neuronal sensation.
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spelling doaj-art-4566caa47f404199853ee3a3653a5ebf2025-08-20T02:32:56ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-07-01207e300171010.1371/journal.pbio.3001710The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.Michael E BaumgartnerAlex MastrogiannopoulosIwo KucinskiPaul F LangtonEugenia PiddiniGustatory Receptor 64 (Gr64) genes are a cluster of 6 neuronally expressed receptors involved in sweet taste sensation in Drosophila melanogaster. Gr64s modulate calcium signalling and excitatory responses to several different sugars. Here, we discover an unexpected nonneuronal function of Gr64 receptors and show that they promote proteostasis in epithelial cells affected by proteotoxic stress. Using heterozygous mutations in ribosome proteins (Rp), which have recently been shown to induce proteotoxic stress and protein aggregates in cells, we show that Rp/+ cells in Drosophila imaginal discs up-regulate expression of the entire Gr64 cluster and depend on these receptors for survival. We further show that loss of Gr64 in Rp/+ cells exacerbates stress pathway activation and proteotoxic stress by negatively affecting autophagy and proteasome function. This work identifies a noncanonical role in proteostasis maintenance for a family of gustatory receptors known for their function in neuronal sensation.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001710&type=printable
spellingShingle Michael E Baumgartner
Alex Mastrogiannopoulos
Iwo Kucinski
Paul F Langton
Eugenia Piddini
The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.
PLoS Biology
title The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.
title_full The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.
title_fullStr The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.
title_full_unstemmed The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.
title_short The Gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in Drosophila.
title_sort gr64 cluster of gustatory receptors promotes survival and proteostasis of epithelial cells in drosophila
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001710&type=printable
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