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Ribosome protein mutant cells rely on the GR64 cluster of gustatory receptors for survival and proteostasis in Drosophila

Michael E. Baumgartner, Iwo Kucinski, View ORCID ProfileEugenia Piddini
doi: https://doi.org/10.1101/2021.05.10.443504
Michael E. Baumgartner
1School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK
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Iwo Kucinski
2The Wellcome Trust/Cancer Research UK Gurdon Institute and Zoology Department, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
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Eugenia Piddini
1School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK
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  • ORCID record for Eugenia Piddini
  • For correspondence: eugenia.piddini@bristol.ac.uk
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Abstract

Mutations in ribosome protein (Rp) genes and ribosome biogenesis factors result in debilitating diseases known as ribosomopathies. Recent studies in Drosophila have shown that cells heterozygous mutant for Rp genes (Rp/+) exhibit proteotoxic stress and aggregates, which drive stress pathway activation and apoptosis. Understanding how Rp/+ cells fend off proteotoxic stress could suggest mechanisms to ameliorate these and other conditions caused by proteotoxic stress. Here we find that Rp/+ epithelial cells express all six Gustatory Receptor 64 (Gr64) genes, a cluster of sugar receptors involved in taste sensation. We show that Rp/+ cells depend on Gr64 for survival and that loss of Gr64 autonomously exacerbates stress pathway activation and proteotoxic stress by negatively effecting autophagy and proteasome function in Rp/+ cells. This work identifies a non-canonical role in proteostasis maintenance for a family of gustatory receptors known for their function in neuronal sensation.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 10, 2021.
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Ribosome protein mutant cells rely on the GR64 cluster of gustatory receptors for survival and proteostasis in Drosophila
Michael E. Baumgartner, Iwo Kucinski, Eugenia Piddini
bioRxiv 2021.05.10.443504; doi: https://doi.org/10.1101/2021.05.10.443504
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Ribosome protein mutant cells rely on the GR64 cluster of gustatory receptors for survival and proteostasis in Drosophila
Michael E. Baumgartner, Iwo Kucinski, Eugenia Piddini
bioRxiv 2021.05.10.443504; doi: https://doi.org/10.1101/2021.05.10.443504

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