AFR1 acts in conjunction with the alpha-factor receptor to promote morphogenesis and adaptation

Mating pheromone receptors activate a G-protein signaling pathway that induces changes in transcription, cell division, and morphogenesis needed for the conjunction of Saccharomyces cerevisiae. The C terminus of the alpha-factor pheromone receptor functions in two complex processes, adaptation and morphogenesis. Adaptation to alpha-factor may occur through receptor desensitization, and alpha-factor-induced morphogenesis forms the conjugation bridge between mating cells. A plasmid overexpression strategy was used to isolate a new gene, AFR1, which acts together with the receptor C terminus to promote adaptation. The expression of AFR1 was highly induced by alpha-factor. Unexpectedly, cells lacking AFR1 showed a defect in alpha-factor-stimulated morphogenesis that was similar to the morphogenesis defect observed in cells producing C-terminally truncated alpha-factor receptors. In contrast, AFR1 overexpression resulted in longer projections of morphogenesis, which suggests that this gene may directly stimulate morphogenesis. These results indicate that AFR1 encodes a developmentally regulated function that coordinates both the regulation of receptor signaling and the induction of morphogenesis during conjugation.

[1]  B. Errede,et al.  Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases , 1993, Molecular and cellular biology.

[2]  H. Riezman,et al.  Yeast pheromone receptor endocytosis and hyperphosphorylation are independent of G protein-mediated signal transduction , 1992, Cell.

[3]  M. Whiteway,et al.  Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  B. Cairns,et al.  Order of action of components in the yeast pheromone response pathway revealed with a dominant allele of the STE11 kinase and the multiple phosphorylation of the STE7 kinase. , 1992, Genes & development.

[5]  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.

[6]  H. Okamura,et al.  Actin- and tubulin-dependent functions during Saccharomyces cerevisiae mating projection formation. , 1992, Molecular biology of the cell.

[7]  I. Herskowitz,et al.  A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains , 1992, Nature.

[8]  M. Snyder,et al.  Cell polarity and morphogenesis in Saccharomyces cerevisiae. , 1992, Trends in cell biology.

[9]  A. Gilman,et al.  G proteins. , 1992, Trends in biochemical sciences.

[10]  G. Fink,et al.  FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Caron,et al.  The receptor kinase family: primary structure of rhodopsin kinase reveals similarities to the beta-adrenergic receptor kinase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. Drubin.  Development of cell polarity in budding yeast , 1991, Cell.

[13]  I. Herskowitz,et al.  Genetic control of bud site selection in yeast by a set of gene products that constitute a morphogenetic pathway , 1991, Cell.

[14]  G F Sprague,et al.  Pheromone response elements are necessary and sufficient for basal and pheromone-induced transcription of the FUS1 gene of Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[15]  K. Irie,et al.  SGV1 encodes a CDC28/cdc2-related kinase required for a Gα subunit-mediated adaptive response to pheromone in S. cerevisiae , 1991, Cell.

[16]  S. Fields,et al.  Pheromone-dependent phosphorylation of the yeast STE12 protein correlates with transcriptional activation. , 1991, Genes & development.

[17]  J. Hirsch,et al.  Mutations in the guanine nucleotide-binding domains of a yeast G alpha protein confer a constitutive or uninducible state to the pheromone response pathway. , 1991, Genes & development.

[18]  S. Reed,et al.  Pheromone-induced phosphorylation of a G protein β subunit in S. cerevisiae is associated with an adaptive response to mating pheromone , 1991, Cell.

[19]  S. Fields,et al.  Cell-type-specific transcription in yeast. , 1991, Biochimica et biophysica acta.

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

[21]  F. Sherman.  Getting started with yeast. , 1991, Methods in enzymology.

[22]  R. Rothstein.  Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. , 1991, Methods in enzymology.

[23]  I. Herskowitz,et al.  Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2 , 1990, Cell.

[24]  J. Navarro,et al.  Molecular cloning of the fMet-Leu-Phe receptor from neutrophils. , 1990, The Journal of biological chemistry.

[25]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[26]  K. Arai,et al.  Regulation of the yeast pheromone response pathway by G protein subunits. , 1990, The EMBO journal.

[27]  S. Reed,et al.  Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway , 1990, Molecular and cellular biology.

[28]  C. Zuker,et al.  Isolation and structure of an arrestin gene from Drosophila. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Whiteway,et al.  Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae , 1990, Molecular and cellular biology.

[30]  S. Fields.  Pheromone response in yeast. , 1990, Trends in biochemical sciences.

[31]  Ira Herskowitz,et al.  A regulatory hierarchy for cell specialization in yeast , 1989, Nature.

[32]  N. Baba,et al.  Three-dimensional analysis of morphogenesis induced by mating pheromone alpha factor in Saccharomyces cerevisiae. , 1989, Journal of cell science.

[33]  J. Thorner,et al.  A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae , 1989, Cell.

[34]  M. Snyder,et al.  The SPA2 protein of yeast localizes to sites of cell growth , 1989, The Journal of cell biology.

[35]  S. Bouvier,et al.  Constitutive mutants in the yeast pheromone response: Ordered function of the gene products , 1989, Cell.

[36]  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.

[37]  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.

[38]  J. Thorner,et al.  The carboxy-terminal segment of the yeast α-factor receptor is a regulatory domain , 1988, Cell.

[39]  T. Hunter,et al.  The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. , 1988, Science.

[40]  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.

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

[42]  G. Saari,et al.  The Saccharomyces cerevisiae BAR1 gene encodes an exported protein with homology to pepsin. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[43]  P. Devreotes,et al.  Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. , 1988, Annual review of cell biology.

[44]  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.

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

[46]  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.

[47]  G. Fink,et al.  Two genes required for cell fusion during yeast conjugation: evidence for a pheromone-induced surface protein , 1987, Molecular and cellular biology.

[48]  D. Botstein,et al.  A Tn10-lacZ-kanR-URA3 gene fusion transposon for insertion mutagenesis and fusion analysis of yeast and bacterial genes. , 1987, Genetics.

[49]  J. Errington.  A general method for fusion of the Escherichia coli lacZ gene to chromosomal genes in Bacillus subtilis. , 1986, Journal of general microbiology.

[50]  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.

[51]  S. W. Hall,et al.  Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[52]  Leland H. Hartwell,et al.  The yeast α-factor receptor: structural properties deduced from the sequence of the STE2 gene , 1985 .

[53]  K. Arai,et al.  Nucleotide sequences of STE2 and STE3, cell type‐specific sterile genes from Saccharomyces cerevisiae , 1985, The EMBO journal.

[54]  J. Devereux,et al.  A comprehensive set of sequence analysis programs for the VAX , 1984, Nucleic Acids Res..

[55]  K. Murata,et al.  Transformation of intact yeast cells treated with alkali cations. , 1984, Journal of bacteriology.

[56]  Leland H. Hartwell,et al.  Binding of α-factor pheromone to yeast a cells: Chemical and genetic evidence for an α-factor receptor , 1983, Cell.

[57]  D. Botstein,et al.  Two differentially regulated mRNAs with different 5′ ends encode secreted and intracellular forms of yeast invertase , 1982, Cell.

[58]  B. Byers.  Cytology of the Yeast Life Cycle , 1981 .

[59]  L. Hartwell.  Mutants of Saccharomyces cerevisiae unresponsive to cell division control by polypeptide mating hormone , 1980, The Journal of cell biology.

[60]  Jeffrey H. Miller.  Experiments in molecular genetics , 1972 .