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.

Hagen, David; McCaffrey, Gretchen; Sprague, G. F.

doi:10.1073/pnas.83.5.1418

Cited by 282 publications

(160 citation statements)

References 34 publications

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“…MATa cells express a-factor (Betz and Duntze 1979), which is secreted through an ATP binding cassette transporter (Ste6) (McGrath and Varshavsky 1989) and the a-factor receptor (Ste2) (Blumer et al 1988;Dohlman and Thorner 2001). MATa cells express a-factor (Kurjan and Herskowitz 1982;Singh et al 1983) and the a-factor receptor (Ste3) (Hagen et al 1986;Dohlman and Thorner 2001). Pheromone binding activates a signaling pathway that produces three responses: cell polarization, cell cycle arrest in G1, and increased transcription of pheromone response genes (Bardwell 2005).…”

mentioning

confidence: 99%

Genetically Engineered Transvestites Reveal Novel Mating Genes in Budding Yeast

Huberman

Murray

2013

Genetics

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Haploid budding yeast has two mating types, defined by the alleles of the MAT locus, MATa and MATa. Two haploid cells of opposite mating types mate by signaling to each other using reciprocal pheromones and receptors, polarizing and growing toward each other, and eventually fusing to form a single diploid cell. The pheromones and receptors are necessary and sufficient to define a mating type, but other mating-type-specific proteins make mating more efficient. We examined the role of these proteins by genetically engineering "transvestite" cells that swap the pheromone, pheromone receptor, and pheromone processing factors of one mating type for another. These cells mate with each other, but their mating is inefficient. By characterizing their mating defects and examining their transcriptomes, we found Afb1 (a-factor barrier), a novel MATa-specific protein that interferes with a-factor, the pheromone secreted by MATa cells. Strong pheromone secretion is essential for efficient mating, and the weak mating of transvestites can be improved by boosting their pheromone production. Synthetic biology can characterize the factors that control efficiency in biological processes. In yeast, selection for increased mating efficiency is likely to have continually boosted pheromone levels and the ability to discriminate between partners who make more and less pheromone. This discrimination comes at a cost: weak mating in situations where all potential partners make less pheromone. BIOLOGICAL processes are typically defined by the genes that are necessary and sufficient for function. However, in many cases, this minimal gene set does not encompass all the proteins involved in a process, and additional proteins promote biological efficiency. Finding these additional proteins may require the detection of subtle phenotypes, making it hard to know if all the genes involved in a process have been identified. One way to answer this question is to reengineer a pathway and ask whether the synthetic version fully mimics the natural function. Here, we show that this form of synthetic biology illuminates how cells of the budding yeast Saccharomyces cerevisiae mate efficiently.Budding yeast can be stably maintained as haploids or diploids. Haploids mate when two cells of opposite mating types signal to each other using reciprocal pheromones and receptors, polarize and grow toward each other, and eventually fuse to form a single diploid. Yeast has two mating types, a and a ( Figure 1A), determined by two alternative alleles at the MAT locus, MATa and MATa, which encode different transcription factors (Herskowitz 1988). These factors regulate the expression of mating-type-specific genes, many of which are involved with the production and detection of the pheromones that yeast cells use to signal to one another. The pheromones (a-and a-factor) are detected by G-proteincoupled receptors. MATa cells express a-factor (Betz and Duntze 1979), which is secreted through an ATP binding cassette transporter (Ste6) (McGrath and Varshavsky 1989)...

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confidence: 99%

Genetically Engineered Transvestites Reveal Novel Mating Genes in Budding Yeast

Huberman

Murray

2013

Genetics

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“…The a cell type produces a unique receptor protein encoded by the STE2 gene, whereas the c~ cell type produces a receptor protein encoded by the STE3 gene. Although the protein sequences encoded by STE2 and STE3 are predicted to have the same structure characteristic of the G-protein-coupled receptors, amino acid similarity between the two receptors is absent [33,205,105]. In S. pombe the two mating types are called h + and h -; the pheromones secreted by these cells are called P-factor and M-factor, respectively.…”

Section: G-protein-coupled Receptorsmentioning

confidence: 99%

Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes

Drayer¹,

Haastert²

1994

Signals and Signal Transduction Pathways in Plants

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“…A large number of these proteins, such as the rhodopsins and adrenergic and muscarinic acetylcholine receptors, form a family based on amino acid homology (e.g., Dohlman et al 1987). In contrast, both the yeast a-and a-factor receptors, which transduce signals in a G protein-dependent fashion, do not have significant amino acid homology to this class or to one another but do contain a similar seven-transmembrane (7 TM) domain motif (Burkolder and Hartwell 1985;Hagen et al 1986). Structural characteristics that are shared by most of the G protein-linked receptors The last extracellular loop is generally small.…”

Section: Genes and Developmentmentioning

confidence: 99%

Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments.

et al. 1990

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Previous genetic mosaic studies established that expression of the Drosophila bride of sevenless (boss) gene is required in photoreceptor neuron R8 for the development of photoreceptor neuron R7. This led to the proposal that boss encodes or regulates an R7-specific inductive cue. We have identified the boss gene based on small deletions in mutant alleles and sequenced both cDNAs and corresponding genomic regions. One P element and three X-ray-induced boss alleles show different deletions in the gene ranging in size from 2 to 23 bp, each causing frameshifts leading to premature termination of translation. The boss gene encodes a protein of 896 amino acids with a putative amino-terminal signal sequence, a large extracellular region of 498 amino acids, and seven potential transmembrane domains followed by a carboxy-terminal cytoplasmic tail of 115 amino acids. The putative membrane localization of the boss protein is consistent with a model in which direct interaction between the boss and sevenless proteins specifies R7 cell fate. Another model in which the boss protein functions as a receptor is proposed based on its similarity to the G protein-linked family of membrane receptors.

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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.

Cited by 282 publications

References 34 publications

Genetically Engineered Transvestites Reveal Novel Mating Genes in Budding Yeast

Genetically Engineered Transvestites Reveal Novel Mating Genes in Budding Yeast

Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes

Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments.

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