Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.

Heterotrimeric G proteins were originally discovered through efforts to understand the effects of hormones, such as glucagon and epinephrine, on glucose metabolism. On the other hand, many cellular metabolites, including glucose, serve as ligands for G protein-coupled receptors. Here we investigate...

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Autores principales:	Shuang Li, Yuanyuan Li, Blake R Rushing, Sarah E Harris, Susan L McRitchie, Janice C Jones, Daniel Dominguez, Susan J Sumner, Henrik G Dohlman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/b1d6d008d7d84ee7807ee27521839932
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spelling	oai:doaj.org-article:b1d6d008d7d84ee7807ee275218399322021-12-02T20:02:47ZMulti-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.1553-73901553-740410.1371/journal.pgen.1009640https://doaj.org/article/b1d6d008d7d84ee7807ee275218399322021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009640https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Heterotrimeric G proteins were originally discovered through efforts to understand the effects of hormones, such as glucagon and epinephrine, on glucose metabolism. On the other hand, many cellular metabolites, including glucose, serve as ligands for G protein-coupled receptors. Here we investigate the consequences of glucose-mediated receptor signaling, and in particular the role of a Gα subunit Gpa2 and a non-canonical Gβ subunit, known as Asc1 in yeast and RACK1 in animals. Asc1/RACK1 is of particular interest because it has multiple, seemingly unrelated, functions in the cell. The existence of such "moonlighting" operations has complicated the determination of phenotype from genotype. Through a comparative analysis of individual gene deletion mutants, and by integrating transcriptomics and metabolomics measurements, we have determined the relative contributions of the Gα and Gβ protein subunits to glucose-initiated processes in yeast. We determined that Gpa2 is primarily involved in regulating carbohydrate metabolism while Asc1 is primarily involved in amino acid metabolism. Both proteins are involved in regulating purine metabolism. Of the two subunits, Gpa2 regulates a greater number of gene transcripts and was particularly important in determining the amplitude of response to glucose addition. We conclude that the two G protein subunits regulate distinct but complementary processes downstream of the glucose-sensing receptor, as well as processes that lead ultimately to changes in cell growth and metabolism.Shuang LiYuanyuan LiBlake R RushingSarah E HarrisSusan L McRitchieJanice C JonesDaniel DominguezSusan J SumnerHenrik G DohlmanPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 7, p e1009640 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Shuang Li Yuanyuan Li Blake R Rushing Sarah E Harris Susan L McRitchie Janice C Jones Daniel Dominguez Susan J Sumner Henrik G Dohlman Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.
description	Heterotrimeric G proteins were originally discovered through efforts to understand the effects of hormones, such as glucagon and epinephrine, on glucose metabolism. On the other hand, many cellular metabolites, including glucose, serve as ligands for G protein-coupled receptors. Here we investigate the consequences of glucose-mediated receptor signaling, and in particular the role of a Gα subunit Gpa2 and a non-canonical Gβ subunit, known as Asc1 in yeast and RACK1 in animals. Asc1/RACK1 is of particular interest because it has multiple, seemingly unrelated, functions in the cell. The existence of such "moonlighting" operations has complicated the determination of phenotype from genotype. Through a comparative analysis of individual gene deletion mutants, and by integrating transcriptomics and metabolomics measurements, we have determined the relative contributions of the Gα and Gβ protein subunits to glucose-initiated processes in yeast. We determined that Gpa2 is primarily involved in regulating carbohydrate metabolism while Asc1 is primarily involved in amino acid metabolism. Both proteins are involved in regulating purine metabolism. Of the two subunits, Gpa2 regulates a greater number of gene transcripts and was particularly important in determining the amplitude of response to glucose addition. We conclude that the two G protein subunits regulate distinct but complementary processes downstream of the glucose-sensing receptor, as well as processes that lead ultimately to changes in cell growth and metabolism.
format	article
author	Shuang Li Yuanyuan Li Blake R Rushing Sarah E Harris Susan L McRitchie Janice C Jones Daniel Dominguez Susan J Sumner Henrik G Dohlman
author_facet	Shuang Li Yuanyuan Li Blake R Rushing Sarah E Harris Susan L McRitchie Janice C Jones Daniel Dominguez Susan J Sumner Henrik G Dohlman
author_sort	Shuang Li
title	Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.
title_short	Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.
title_full	Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.
title_fullStr	Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.
title_full_unstemmed	Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.
title_sort	multi-omics analysis of glucose-mediated signaling by a moonlighting gβ protein asc1/rack1.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b1d6d008d7d84ee7807ee27521839932
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Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.

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