Multiple sex pheromones and receptors of a mushroom-producing fungus elicit mating in yeast.

The mushroom-producing fungus Schizophyllum commune has thousands of mating types defined, in part, by numerous lipopeptide pheromones and their G protein-linked receptors. Compatible combinations of pheromones and receptors encoded by different mating types regulate a pathway of sexual development leading to mushroom formation and meiosis. A complex set of pheromone-receptor interactions maximizes the likelihood of outbreeding; for example, a single pheromone can activate more than one receptor and a single receptor can be activated by more than one pheromone. The current study demonstrates that the sex pheromones and receptors of Schizophyllum, when expressed in Saccharomyces cerevisiae, can substitute for endogenous pheromone and receptor and induce the yeast pheromone response pathway through the yeast G protein. Secretion of active Schizophyllum pheromone requires some, but not all, of the biosynthetic machinery used by the yeast lipopeptide pheromone a-factor. The specificity of interaction among pheromone-receptor pairs in Schizophyllum was reproduced in yeast, thus providing a powerful system for exploring molecular aspects of pheromone-receptor interactions for a class of seven-transmembrane-domain receptors common to a wide range of organisms.

[1]  J. Kurjan The pheromone response pathway in Saccharomyces cerevisiae. , 1993, Annual review of genetics.

[2]  I. Rodriguez,et al.  Variable Patterns of Axonal Projections of Sensory Neurons in the Mouse Vomeronasal System , 1999, Cell.

[3]  C. Specht,et al.  Multiple genes encoding pheromones and a pheromone receptor define the B beta 1 mating-type specificity in Schizophyllum commune. , 1997, Genetics.

[4]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[5]  Y. Koltin,et al.  Alteration of nuclear distribution in B-mutant strains of Schizophyllum commune. , 1969, Journal of cell science.

[6]  J. Kurjan,et al.  The yeast SCG1 gene: A Gα-like protein implicated in the a- and α-factor response pathway , 1987, Cell.

[7]  The yeast SCG1 gene: a G alpha-like protein implicated in the a- and alpha-factor response pathway. , 1987, Cell.

[8]  G. Simchen,et al.  The genetic structure of the incompatibility factors of Schizophyllum commune: the B factor. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[9]  E. Kothe,et al.  The mating‐type locus B alpha 1 of Schizophyllum commune contains a pheromone receptor gene and putative pheromone genes. , 1995, The EMBO journal.

[10]  Comparison of dose-response curves for alpha factor-induced cell division arrest, agglutination, and projection formation of yeast cells. Implication for the mechanism of alpha factor action. , 1983, The Journal of biological chemistry.

[11]  N. Ryba,et al.  Putative Mammalian Taste Receptors A Class of Taste-Specific GPCRs with Distinct Topographic Selectivity , 1999, Cell.

[12]  I. Herskowitz,et al.  Negative regulation of STE6 gene expression by the alpha 2 product of Saccharomyces cerevisiae , 1984, Molecular and cellular biology.

[13]  F. Cross,et al.  The Pheromone Receptors Inhibit the Pheromone Response Pathway in Saccharomyces cerevisiae by a Process That Is Independent of Their Associated Ga! Protein , 2002 .

[14]  Sangram S. Sisodia,et al.  Dual Roles for Ste24p in Yeast a-Factor Maturation: NH2-terminal Proteolysis and COOH-terminal CAAX Processing , 1998, The Journal of cell biology.

[15]  J. Hirsch,et al.  Receptor Inhibition of Pheromone Signaling Is Mediated by the Ste4p Gβ Subunit , 1999, Molecular and Cellular Biology.

[16]  C. Raper,et al.  Mutational analysis of a regulatory gene for morphogenesis in Schizophyllum. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[17]  S. Carr,et al.  Structure of Saccharomyces cerevisiae mating hormone a-factor. Identification of S-farnesyl cysteine as a structural component. , 1988, The Journal of biological chemistry.

[18]  R. Axel,et al.  A novel family of genes encoding putative pheromone receptors in mammals , 1995, Cell.

[19]  L. Casselton,et al.  Molecular Genetics of Mating Recognition in Basidiomycete Fungi , 1998, Microbiology and Molecular Biology Reviews.

[20]  J. Thorner,et al.  Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. , 1989, The EMBO journal.

[21]  J. Kurjan,et al.  Pheromonal regulation and sequence of the Saccharomyces cerevisiae SST2 gene: a model for desensitization to pheromone. , 1987, Molecular and cellular biology.

[22]  Raudaskoski The relationship between B-mating-type genes and nuclear migration in schizophyllum commune , 1998, Fungal genetics and biology : FG & B.

[23]  J. Rine,et al.  Modulation of Ras and a-Factor Function by Carboxyl-Terminal Proteolysis , 1997, Science.

[24]  S. Reed,et al.  Mutations in a gene encoding the alpha subunit of a Saccharomyces cerevisiae G protein indicate a role in mating pheromone signaling , 1988, Molecular and cellular biology.

[25]  A. Varshavsky,et al.  The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein , 1989, Nature.

[26]  G. Fink,et al.  The yeast cell fusion protein FUS1 is O-glycosylated and spans the plasma membrane. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[27]  V. Lundblad,et al.  Preparation of Yeast Media , 1993, Current protocols in molecular biology.

[28]  S. Reed,et al.  A G-protein alpha subunit from asexual Candida albicans functions in the mating signal transduction pathway of Saccharomyces cerevisiae and is regulated by the a1-alpha 2 repressor , 1992, Molecular and cellular biology.

[29]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[30]  J. Wessels,et al.  ENZYMIC DEGRADATION OF SEPTA IN HYPHAL WALL PREPARATIONS FROM A MONOKARYON AND A DIKARYON OF SCHIZOPHYLLUM-COMMUNE , 1974 .

[31]  R. Axel,et al.  A Map of Pheromone Receptor Activation in the Mammalian Brain , 1999, Cell.

[32]  M. Whiteway,et al.  The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein. , 1989, Cell.

[33]  B. Ozenberger,et al.  Functional coupling of a mammalian somatostatin receptor to the yeast pheromone response pathway , 1995, Molecular and cellular biology.

[34]  A. Ellingboe,et al.  THE GENETIC STRUCTURE OF THE INCOMPATIBILITY FACTORS OF SCHIZOPHYLLUM COMMUNE: THE A-FACTOR. , 1960, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Taosheng Chen,et al.  Saccharomyces cerevisiae Mpt5p interacts with Sst2p and plays roles in pheromone sensitivity and recovery from pheromone arrest , 1997, Molecular and cellular biology.

[36]  G. Sprague,,et al.  Pheromones and pheromone receptors are the primary determinants of mating specificity in the yeast Saccharomyces cerevisiae. , 1989, Genetics.

[37]  S. Michaelis,et al.  Nucleotide sequence of the yeast STE14 gene, which encodes farnesylcysteine carboxyl methyltransferase, and demonstration of its essential role in a-factor export , 1994, Molecular and cellular biology.

[38]  J. Raper Genetics of Sexuality in Higher Fungi , 1967 .

[39]  P. Chen,et al.  A novel a-factor-related peptide of Saccharomyces cerevisiae that exits the cell by a Ste6p-independent mechanism. , 1997, Molecular biology of the cell.

[40]  D. Dorris,et al.  Yeast Vectors and Assays for Expression of Cloned Genes , 1997, Current protocols in molecular biology.

[41]  S. Michaelis,et al.  Biogenesis of the Saccharomyces cerevisiae Mating Pheromone a-Factor , 1997, The Journal of cell biology.

[42]  J. Thorner,et al.  RGS Proteins and Signaling by Heterotrimeric G Proteins* , 1997, The Journal of Biological Chemistry.

[43]  C. Boone,et al.  Role of Yeast Insulin-Degrading Enzyme Homologs in Propheromone Processing and Bud Site Selection , 1995, Science.

[44]  J. Raper,et al.  THE GENETIC STRUCTURE OF THE INCOMPATIBILITY FACTORS IN SCHIZOPHYLLIUM COMMUNE. , 1958, Proceedings of the National Academy of Sciences of the United States of America.

[45]  K. Arai,et al.  GPA1, a haploid-specific essential gene, encodes a yeast homolog of mammalian G protein which may be involved in mating factor signal transduction , 1987, Cell.

[46]  T. Bisseling,et al.  Isolation of total and polysomal RNA from plant tissues , 1989 .

[47]  S. Michaelis,et al.  A Novel Membrane-associated Metalloprotease, Ste24p, Is Required for the First Step of NH2-terminal Processing of the Yeast a-Factor Precursor , 1997, The Journal of cell biology.

[48]  W. Schafer,et al.  Protein prenylation: genes, enzymes, targets, and functions. , 1992, Annual review of genetics.

[49]  F. Cross,et al.  ‘Marker Swap’ Plasmids: Convenient Tools for Budding Yeast Molecular Genetics , 1997 .

[50]  L. Vaillancourt,et al.  Pheromones and pheromone receptors as mating-type determinants in basidiomycetes. , 1996, Genetic engineering.

[51]  R. K. Chan,et al.  Isolation and genetic analysis of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by a factor and alpha factor pheromones , 1982, Molecular and cellular biology.

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

[53]  G. Sprague,,et al.  Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor: gene sequence and implications for the structure of the presumed receptor. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Y. Kang,et al.  Effects of expression of mammalian G alpha and hybrid mammalian-yeast G alpha proteins on the yeast pheromone response signal transduction pathway , 1990, Molecular and cellular biology.

[55]  J. Becker,et al.  Significance of C-terminal cysteine modifications to the biological activity of the Saccharomyces cerevisiae a-factor mating pheromone , 1991, Molecular and cellular biology.

[56]  D. Taglicht,et al.  Saccharomyces cerevisiae ABC proteins and their relevance to human health and disease. , 1998, Methods in enzymology.

[57]  S. Powers,et al.  RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[58]  R. Schilperoort,et al.  Plant Molecular Biology Manual , 1989, Springer Netherlands.

[59]  J. Thorner,et al.  12 Pheromone Response and Signal Transduction during the Mating Process of Saccharomyces cerevisiae , 1992 .

[60]  I. Herskowitz,et al.  The a-factor pheromone of Saccharomyces cerevisiae is essential for mating , 1988, Molecular and cellular biology.