Pro-Aging Effects of Glucose Signaling through a G Protein-Coupled Glucose Receptor in Fission Yeast

Abstract Most sexually reproducing organisms have the ability to recognize individuals of the same species. In ascomycete fungi including yeasts, mating between cells of opposite mating type depends on the molecular recognition of two peptidyl mating pheromones by their corresponding G-protein coupled receptors (GPCRs). Although such pheromone/receptor systems are likely to function in both mate choice and prezygotic isolation, very few studies have focused on the stringency of pheromone receptors. The fission yeast Schizosaccharomyces pombe has two mating types, Plus (P) and Minus (M). Here we investigated the stringency of the two GPCRs, Mam2 and Map3, for their respective pheromones, P-factor and M-factor, in fission yeast. First, we switched GPCRs between S. pombe and the closely related species Schizosaccharomyces octosporus, which showed that SoMam2 (Mam2 of S. octosporus) is partially functional in S. pombe, whereas SoMap3 (Map3 of S. octosporus) is not interchangeable. Next, we swapped individual domains of Mam2 and Map3 with the respective domains in SoMam2 and SoMap3, which revealed differences between the receptors both in the intracellular regions that regulate the downstream signaling of pheromones and in the activation by the pheromone. In particular, we demonstrated that two amino acid residues of Map3, F214 and F215, are key residues important for discrimination of closely related M-factors. Thus, the differences in these two GPCRs might reflect the significantly distinct stringency/flexibility of their respective pheromone/receptor systems; nevertheless, species-specific pheromone recognition remains incomplete.

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Multi-omics analysis of multiple glucose-sensing receptor systems in yeast

10.1101/2021.10.07.463466 ◽

2021 ◽

Author(s):

Shuang Li ◽

Yuanyuan Li ◽

Blake R. Rushing ◽

Sarah E. Harris ◽

Susan L. McRitchie ◽

...

Keyword(s):

G Protein ◽

Molecular Basis ◽

Glucose Sensing ◽

Glucose Detection ◽

Yeast Saccharomyces Cerevisiae ◽

Glucose Signaling ◽

Cognate Receptor ◽

Small G Protein ◽

Dependent Signal ◽

G Protein Coupled

The yeast Saccharomyces cerevisiae has long been used to produce alcohol from glucose and other sugars. While much is known about glucose metabolism, relatively little is known about the receptors and signaling pathways that indicate glucose availability. Here we compare the two glucose receptor systems in S. cerevisiae. The first is a heterodimer of transporter-like proteins (transceptors), while the second is a seven-transmembrane receptor coupled to a large G protein (Gpa2) and two small G proteins (Ras1 and Ras2). Through comprehensive measurements of glucose-dependent transcription and metabolism, we demonstrate that the two receptor systems have distinct roles in glucose signaling: the G protein-coupled receptor directs carbohydrate and energy metabolism, while the transceptors regulate ancillary processes such as ribosome, amino acids, cofactor and vitamin metabolism. The large G protein transmits the signal from its cognate receptor, while the small G protein Ras2 (but not Ras1) integrates responses from both receptor pathways. Collectively, our analysis reveals the molecular basis for glucose detection and the earliest events of glucose-dependent signal transduction in yeast.

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Glucose Monitoring in Fission Yeast via the gpa2 Gα, the git5 Gβ and the git3 Putative Glucose Receptor

Genetics ◽

10.1093/genetics/156.2.513 ◽

2000 ◽

Vol 156 (2) ◽

pp. 513-521

Author(s):

Robert M Welton ◽

Charles S Hoffman

Keyword(s):

Adenylate Cyclase ◽

Fission Yeast ◽

G Protein ◽

Glucose Repression ◽

Glucose Monitoring ◽

Coding Region ◽

Guanine Nucleotide Binding Protein ◽

Cyclase Activation ◽

Adenylate Cyclase Activation ◽

G Protein Coupled

Abstract The fission yeast Schizosaccharomyces pombe responds to environmental glucose by activating adenylate cyclase. The resulting cAMP signal activates protein kinase A (PKA). PKA inhibits glucose starvation-induced processes, such as conjugation and meiosis, and the transcription of the fbp1 gene that encodes the gluconeogenic enzyme fructose-1,6-bisphosphatase. We previously identified a collection of git genes required for glucose repression of fbp1 transcription, including pka1/git6, encoding the PKA catalytic subunit, git2/cyr1, encoding adenylate cyclase, and six “upstream” genes required for adenylate cyclase activation. The git8 gene, identical to gpa2, encodes the alpha subunit of a heterotrimeric guanine-nucleotide binding protein (Gα) while git5 encodes a Gβ subunit. Multicopy suppression studies with gpa2+ previously indicated that S. pombe adenylate cyclase activation may resemble that of the mammalian type II enzyme with sequential activation by Gα followed by βγ. We show here that an activated allele of gpa2 (gpa2R176H, carrying a mutation in the coding region for the GTPase domain) fully suppresses mutations in git3 and git5, leading to a refinement in our model. We describe the cloning of git3 and show that it encodes a putative seven-transmembrane G protein-coupled receptor. A git3 deletion confers the same phenotypes as deletions of other components of the PKA pathway, including a germination delay, constitutive fbp1 transcription, and starvation-independent conjugation. Since the git3 deletion is fully suppressed by the gpa2R176H allele with respect to fbp1 transcription, git3 appears to encode a G protein-coupled glucose receptor responsible for adenylate cyclase activation in S. pombe.

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Combined use of two transcriptional reporters improves signalling assays for G protein-coupled receptors in fission yeast

Yeast ◽

10.1002/yea.1402 ◽

2006 ◽

Vol 23 (12) ◽

pp. 889-897 ◽

Cited By ~ 1

Author(s):

Anamika Das ◽

Rachel Forfar ◽

Graham Ladds ◽

John Davey

Keyword(s):

Fission Yeast ◽

G Protein ◽

G Protein Coupled Receptors ◽

Combined Use ◽

G Protein Coupled

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Author response for "Estrogen receptor alpha, g‐protein coupled receptor 1, and aromatase: developmental, sex, and region‐specific differences across the rat caudate‐putamen, nucleus accumbens core and shell"

10.1002/cne.24978/v4/response1 ◽

2020 ◽

Author(s):

Amanda A. Krentzel ◽

Jaime A. Willett ◽

Ashlyn G. Johnson ◽

John Meitzen

Keyword(s):

Estrogen Receptor ◽

Nucleus Accumbens ◽

G Protein ◽

Estrogen Receptor Alpha ◽

Author Response ◽

G Protein Coupled Receptor ◽

Nucleus Accumbens Core ◽

Caudate Putamen ◽

Receptor Alpha ◽

G Protein Coupled

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Author response for "Estrogen receptor alpha, g‐protein coupled receptor 1, and aromatase: developmental, sex, and region‐specific differences across the rat caudate‐putamen, nucleus accumbens core and shell"

10.1002/cne.24978/v3/response1 ◽

2020 ◽

Author(s):

Amanda A. Krentzel ◽

Jaime A. Willett ◽

Ashlyn G. Johnson ◽

John Meitzen

Keyword(s):

Estrogen Receptor ◽

Nucleus Accumbens ◽

G Protein ◽

Estrogen Receptor Alpha ◽

Author Response ◽

G Protein Coupled Receptor ◽

Nucleus Accumbens Core ◽

Caudate Putamen ◽

Receptor Alpha ◽

G Protein Coupled

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A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

Clinical Science ◽

10.1042/cs20190579 ◽

2020 ◽

Vol 134 (5) ◽

pp. 473-512 ◽

Cited By ~ 5

Author(s):

Ryan P. Ceddia ◽

Sheila Collins

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

Signaling Pathways ◽

G Protein ◽

Uncoupling Protein ◽

Beige Adipocytes ◽

Nucleotide Regulation ◽

Ucp1 Expression ◽

Thermogenic Adipocytes ◽

G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

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