The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae.

Pseudohyphal differentiation in the budding yeast Saccharomyces cerevisiae is induced in diploid cells in response to nitrogen starvation and abundant fermentable carbon source. Filamentous growth requires at least two signaling pathways: the pheromone responsive MAP kinase cascade and the Gpa2p-cAMP-PKA signaling pathway. Recent studies have established a physical and functional link between the Galpha protein Gpa2 and the G protein-coupled receptor homolog Gpr1. We report here that the Gpr1 receptor is required for filamentous and haploid invasive growth and regulates expression of the cell surface flocculin Flo11. Epistasis analysis supports a model in which the Gpr1 receptor regulates pseudohyphal growth via the Gpa2p-cAMP-PKA pathway and independently of both the MAP kinase cascade and the PKA related kinase Sch9. Genetic and physiological studies indicate that the Gpr1 receptor is activated by glucose and other structurally related sugars. Because expression of the GPR1 gene is known to be induced by nitrogen starvation, the Gpr1 receptor may serve as a dual sensor of abundant carbon source (sugar ligand) and nitrogen starvation. In summary, our studies reveal a novel G protein-coupled receptor senses nutrients and regulates the dimorphic transition to filamentous growth via a Galpha protein-cAMP-PKA signal transduction cascade.

[1]  F. Sherman.  Getting started with yeast. , 2002, Methods in enzymology.

[2]  G. Fink,et al.  Ssy1p and Ptr3p Are Plasma Membrane Components of a Yeast System That Senses Extracellular Amino Acids , 1999, Molecular and Cellular Biology.

[3]  J. Heitman,et al.  Cyclic AMP-Dependent Protein Kinase Regulates Pseudohyphal Differentiation in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[4]  Simon C Watkins,et al.  Std1 and Mth1 Proteins Interact with the Glucose Sensors To Control Glucose-Regulated Gene Expression in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[5]  B. Turcq,et al.  MOD-D, a Galpha subunit of the fungus Podospora anserina, is involved in both regulation of development and vegetative incompatibility. , 1999, Genetics.

[6]  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.

[7]  G. Fink,et al.  Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae. , 1999, Molecular biology of the cell.

[8]  G. Fink,et al.  MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene , 1999, The EMBO journal.

[9]  B. André,et al.  Amino Acid Signaling in Saccharomyces cerevisiae: a Permease-Like Sensor of External Amino Acids and F-Box Protein Grr1p Are Required for Transcriptional Induction of the AGP1 Gene, Which Encodes a Broad-Specificity Amino Acid Permease , 1999, Molecular and Cellular Biology.

[10]  M. Bölker.  Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis. , 1998, Fungal genetics and biology : FG & B.

[11]  J. Heitman,et al.  Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains. , 1998, Genetics.

[12]  J. Broach,et al.  Efficient transition to growth on fermentable carbon sources in Saccharomyces cerevisiae requires signaling through the Ras pathway , 1998, The EMBO journal.

[13]  G. Fink,et al.  The three yeast A kinases have specific signaling functions in pseudohyphal growth. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Kumagai,et al.  Gpr1p, a putative G-protein coupled receptor, regulates glucose-dependent cellular cAMP level in yeast Saccharomyces cerevisiae. , 1998, Biochemical and biophysical research communications.

[15]  R. Kahmann,et al.  Crosstalk between cAMP and pheromone signalling pathways in Ustilago maydis , 1998, Molecular and General Genetics MGG.

[16]  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.

[17]  Mark Johnston,et al.  Glucose sensing and signaling by two glucose receptors 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.  The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae , 1998, The EMBO journal.

[20]  B. Regenberg,et al.  The permease homologue Ssy1p controls the expression of amino acid and peptide transporter genes in Saccharomyces cerevisiae , 1998, Molecular microbiology.

[21]  W. Lo,et al.  The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae. , 1998, Molecular biology of the cell.

[22]  J. Heitman,et al.  Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP. , 1997, Genes & development.

[23]  Gerald R. Fink,et al.  MAP Kinases with Distinct Inhibitory Functions Impart Signaling Specificity during Yeast Differentiation , 1997, Cell.

[24]  H. Kumagai,et al.  G-protein coupled receptor from yeast Saccharomyces cerevisiae. , 1997, Biochemical and biophysical research communications.

[25]  L. Bardwell,et al.  Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous- growth signalling pathway , 1997, Nature.

[26]  S. Kron.  Filamentous growth in budding yeast. , 1997, Trends in microbiology.

[27]  A. Lichter,et al.  Fil1, a G-protein α-subunit that acts upstream of cAMP and is essential for dimorphic switching in haploid cells of Ustilago hordei , 1997, Molecular and General Genetics MGG.

[28]  G. Fink,et al.  Nonfilamentous C. albicans Mutants Are Avirulent , 1997, Cell.

[29]  M. Lisanti,et al.  Gpa2p, a G-protein α-Subunit, Regulates Growth and Pseudohyphal Development in Saccharomyces cerevisiae via a cAMP-dependent Mechanism* , 1997, The Journal of Biological Chemistry.

[30]  C. Michels,et al.  Two glucose sensing/signaling pathways stimulate glucose-induced inactivation of maltose permease in Saccharomyces. , 1997, Molecular biology of the cell.

[31]  G. Guidotti,et al.  Glucose-dependent, cAMP-mediated ATP efflux from Saccharomyces cerevisiae. , 1997, Microbiology.

[32]  D. Ebbole,et al.  rco-3, a gene involved in glucose transport and conidiation in Neurospora crassa. , 1997, Genetics.

[33]  M. Bölker,et al.  G proteins in Ustilago maydis: transmission of multiple signals? , 1997, The EMBO journal.

[34]  J. Heitman,et al.  Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog. , 1997, The EMBO journal.

[35]  H. Liang,et al.  A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6. , 1996, Molecular biology of the cell.

[36]  S. Wölfl,et al.  Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[37]  J. Ramírez,et al.  Isolation of a gene encoding a G protein α subunit involved in the regulation of cAMP levels in the yeast Kluyveromyces lactis , 1996, Yeast.

[38]  I. S. Pretorius,et al.  Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[39]  G. Fink,et al.  Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[40]  B. Stillman,et al.  Cold Spring Harbor Laboratory , 1995, Molecular medicine.

[41]  C. Parent,et al.  Molecular genetics of signal transduction in Dictyostelium. , 1996, Annual review of biochemistry.

[42]  G. Fink,et al.  SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription , 1995, Molecular and cellular biology.

[43]  E. Neer.  Heterotrimeric C proteins: Organizers of transmembrane signals , 1995, Cell.

[44]  G. Fink,et al.  Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth. , 1994, Genes & development.

[45]  P. Philippsen,et al.  New heterologous modules for classical or PCR‐based gene disruptions in Saccharomyces cerevisiae , 1994, Yeast.

[46]  J. Chenevert,et al.  Cell polarization directed by extracellular cues in yeast. , 1994, Molecular biology of the cell.

[47]  M. Yamamoto,et al.  Glucose repression of fbp1 transcription of Schizosaccharomyces pombe is partially regulated by adenylate cyclase activation by a G protein alpha subunit encoded by gpa2 (git8). , 1994, Genetics.

[48]  J. Thevelein,et al.  Possible involvement of a phosphatidylinositol-type signaling pathway in glucose-induced activation of plasma membrane H(+)-ATPase and cellular proton extrusion in the yeast Saccharomyces cerevisiae. , 1994, Biochimica et biophysica acta.

[49]  G. Fink,et al.  Induction of pseudohyphal growth by overexpression of PHD1, a Saccharomyces cerevisiae gene related to transcriptional regulators of fungal development , 1994, Molecular and cellular biology.

[50]  G. Fink,et al.  Elements of the yeast pheromone response pathway required for filamentous growth of diploids. , 1993, Science.

[51]  J. Segall,et al.  Polarization of yeast cells in spatial gradients of alpha mating factor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[52]  P. Hawkins,et al.  Analysis of inositol metabolites produced by Saccharomyces cerevisiae in response to glucose stimulation. , 1993, Journal of Biological Chemistry.

[53]  M. Yamamoto,et al.  Characterization of a fission yeast gene, gpa2, that encodes a G alpha subunit involved in the monitoring of nutrition. , 1992, Genes & development.

[54]  B. Errede,et al.  Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. , 1992, Genes & development.

[55]  Gerald R. Fink,et al.  Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: Regulation by starvation and RAS , 1992, Cell.

[56]  R. Reed,et al.  Signaling pathways in odorant detection , 1992, Neuron.

[57]  L. Hartwell,et al.  S. cerevisiae α pheromone receptors activate a novel signal transduction pathway for mating partner discrimination , 1991, Cell.

[58]  F. Winston,et al.  Glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene occurs by a cAMP signaling pathway. , 1991, Genes & development.

[59]  J. Broach,et al.  RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway. , 1991, Trends in genetics : TIG.

[60]  J. Thorner,et al.  Control of yeast mating signal transduction by a mammalian beta 2-adrenergic receptor and Gs alpha subunit. , 1990, Science.

[61]  F. Winston,et al.  Isolation and characterization of mutants constitutive for expression of the fbp1 gene of Schizosaccharomyces pombe. , 1990, Genetics.

[62]  R. D. Gietz,et al.  New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. , 1988, Gene.

[63]  M. Wigler,et al.  SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits. , 1988, Genes & development.

[64]  K. Arai,et al.  Isolation of a second yeast Saccharomyces cerevisiae gene (GPA2) coding for guanine nucleotide-binding regulatory protein: studies on its structure and possible functions. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[65]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[66]  Ramón Serrano,et al.  In vivo glucose activation of the yeast plasma membrane ATPase , 1983, FEBS letters.

[67]  G. Fink,et al.  Ras 2 signals via the Cdc 42 / Ste 20 / mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae , 2022 .