Sex and sugar in yeast: two distinct GPCR systems

Although eukaryotic G‐protein coupled receptor (GPCR) systems are well known for their ability to detect and mediate rapid responses to extracellular signals, the full range of stimuli to which they respond may not yet have been identified. Activation of GPCRs by hormones, pheromones, odorants, neurotransmitters, light and different taste compounds is well established. However, the recent discovery of a glucose‐sensing GPCR system in Saccharomyces cerevisiae has unexpectedly added common nutrients to this list of stimuli. This GPCR system mediates glucose activation of adenylate cyclase during the switch from respirative/gluconeogenic metabolism to fermentation. The GPCR system involved in pheromone signalling in S. cerevisiae has already served as an important model and tool for the study of GPCR systems in higher eukaryotic cell types. Here, we highlight the similarities and differences between these two signalling systems. We also indicate how the new glucose‐sensing system can serve as a model for GPCR function and as a tool with which to screen for heterologous components of signalling pathways as well as for novel ligands in high‐throughput assays.

[1]  C. S. Hoffman,et al.  The git5 Gbeta and git11 Ggamma form an atypical Gbetagamma dimer acting in the fission yeast glucose/cAMP pathway. , 2001, Genetics.

[2]  M. Whiteway,et al.  Transcriptional control of cell type and morphogenesis in Candida albicans. , 2000, Current opinion in microbiology.

[3]  S. Colombo,et al.  A baker's yeast mutant (fil1) with a specific, partially inactivating mutation in adenylate cyclase maintains a high stress resistance during active fermentation and growth. , 2000, Journal of molecular microbiology and biotechnology.

[4]  C. S. Hoffman,et al.  Glucose monitoring in fission yeast via the Gpa2 galpha, the git5 Gbeta and the git3 putative glucose receptor. , 2000, Genetics.

[5]  J. D. de Winde,et al.  Glucose‐induced cAMP signalling in yeast requires both a G‐protein coupled receptor system for extracellular glucose detection and a separable hexose kinase‐dependent sensing process , 2000, Molecular microbiology.

[6]  P. Defossez,et al.  Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. , 2000, Science.

[7]  J. Heitman,et al.  The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. , 2000, Genetics.

[8]  M. Marzioch,et al.  Functional coupling of mammalian receptors to the yeast mating pathway using novel yeast/mammalian G protein α‐subunit chimeras , 2000, Yeast.

[9]  C. S. Hoffman,et al.  Glucose Monitoring in Fission Yeast via the gpa2 Ga, the git5 Gb and the git3 Putative Glucose Receptor , 2000 .

[10]  R. Aebersold,et al.  Feedback Phosphorylation of an RGS Protein by MAP Kinase in Yeast* , 1999, The Journal of Biological Chemistry.

[11]  J. D. de Winde,et al.  A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose‐activation of the cAMP pathway through direct inhibition of Gpa2 , 1999, The EMBO journal.

[12]  W. Bandlow,et al.  The Yeast Trimeric Guanine Nucleotide-Binding Protein α Subunit, Gpa2p, Controls the Meiosis-Specific Kinase Ime2p Activity in Response to Nutrients , 1999, Molecular and Cellular Biology.

[13]  E. Duzic,et al.  Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling , 1999, Nature Biotechnology.

[14]  J. D. de Winde,et al.  A Saccharomyces cerevisiae G‐protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose , 1999, Molecular microbiology.

[15]  Temple F. Smith,et al.  The WD repeat: a common architecture for diverse functions. , 1999, Trends in biochemical sciences.

[16]  S. Sprang,et al.  Structural basis of activity and subunit recognition in G protein heterotrimers. , 1998, Structure.

[17]  J. D. de Winde,et al.  Involvement of distinct G‐proteins, Gpa2 and Ras, in glucose‐ and intracellular acidification‐induced cAMP signalling in the yeast Saccharomyces cerevisiae , 1998, The EMBO journal.

[18]  J. Hirsch,et al.  GPR1 encodes a putative G protein‐coupled receptor that associates with the Gpa2p Gα subunit and functions in a Ras‐independent pathway , 1998, The EMBO journal.

[19]  J. Heitman,et al.  Yeast pseudohyphal growth is regulated by GPA2, a G protein α homolog , 1997 .

[20]  M. Pausch,et al.  G-protein-coupled receptors in Saccharomyces cerevisiae: high-throughput screening assays for drug discovery. , 1997, Trends in biotechnology.

[21]  D. Bergsma,et al.  Orphan G protein-coupled receptors: a neglected opportunity for pioneer drug discovery. , 1997, Trends in pharmacological sciences.

[22]  S. Sprang,et al.  Structure of the GDP–Pi complex of Gly203→Ala Giα1: a mimic of the ternary product complex of Gα-catalyzed GTP hydrolysis , 1996 .

[23]  J. Thorner,et al.  Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein alpha subunit) , 1996, Molecular and cellular biology.

[24]  M. Whiteway,et al.  The protein kinase homologue Ste20p is required to link the yeast pheromone response G‐protein beta gamma subunits to downstream signalling components. , 1992, The EMBO journal.

[25]  M. Whiteway,et al.  Theprotein kinase homologue Ste2Opisrequired tolink theyeastpheromone response G-protein flysubunits to downstream signalling components , 1992 .

[26]  J. Thevelein Fermentable sugars and intracellular acidification as specific activators of the RAS‐adenylate cyclase signalling pathway in yeast: the relationship to nutrient‐induced cell cycle control , 1991, Molecular microbiology.

[27]  J. Thorner,et al.  Model systems for the study of seven-transmembrane-segment receptors. , 1991, Annual review of biochemistry.

[28]  David Y. Thomas,et al.  The STE4 and STE18 genes of yeast encode potential β and γ subunits of the mating factor receptor-coupled G protein , 1989, Cell.

[29]  J M Thevelein,et al.  Studies on the mechanism of the glucose-induced cAMP signal in glycolysis and glucose repression mutants of the yeast Saccharomyces cerevisiae. , 1988, European journal of biochemistry.

[30]  M. Nakafuku,et al.  Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA coding for the alpha subunit of mammalian G proteins. , 1987, Proceedings of the National Academy of Sciences of the United States of America.