2. The mating pathway is triggered by signal transduction

17.2 The mating pathway is triggered by signal transduction


The yeast S. cerevisiae can propagate happily in either the haploid or diploid condition. Conversion between these states takes place by mating (fusion of haploid spores to give a diploid) and by sporulation (meiosis of diploids to give haploid spores). The ability to engage in these activities is determined by the mating type of the strain.




Figure 17.1 Mating type controls several activities.

The properties of the two mating types are summarized in Figure 17.1. We may view them as resting on the teleological proposition that there is no point in mating unless the haploids are of different genetic types; and sporulation is productive only when the diploid is heterozygous and thus can generate recombinants.


The mating type of a (haploid) cell is determined by the genetic information present at the MAT locus. Cells that carry the MATa allele at this locus are type a; likewise, cells that carry the MATα allele are type α. Cells of opposite types can mate; cells of the same type cannot.


Recognition of cells of opposite mating type is accomplished by the secretion of pheromones. α cells secrete the small polypeptide α-factor; a cells secrete a-factor. The α-factor is a peptide of 13 amino acids; the a-factor is a peptide of 12 amino acids that is modified by addition of a farnesyl (lipid-like) group and carboxymethylation. Each of these peptides is synthesized in the form of a precursor polypeptide that is cleaved to release the mature peptide sequence.


A cell of one mating type carries a surface receptor for the pheromone of the opposite type. When an a cell and an α cell encounter one another, their pheromones act on each other to arrest the cells in the G1 phase of the cell cycle, and various morphological changes occur. In a successful mating, the cell cycle arrest is followed by cell and nuclear fusion to produce an a/α diploid cell.




Figure 17.2 The yeast life cycle proceeds through mating of MATa and MATa haploids to give heterozygous diploids that sporulate to generate haploid spores.

The a/α cell carries both the MATa and MATα alleles and has the ability to sporulate. Figure 17.2 demonstrates how this design maintains the normal haploid/diploid life cycle. Note that only heterozygous diploids can sporulate; homozygous diploids (either a/a or α/α) cannot sporulate.>


Much of the information about the yeast mating type pathway was deduced from the properties of mutations that eliminate the ability of a and/or α cells to mate. The genes identified by such mutations are called STE (for sterile). Mutations in the genes STE2 and STE3 are specific for individual mating types; but mutations in the other STE genes eliminate mating in both a and α cells. This situation is explained by the idea that the events that follow the interaction of factor with receptor are identical for both types (for review see Nasmyth, 1982).


Mating is a symmetrical process that is initiated by the interaction of pheromone secreted by one cell type with the receptor carried by the other cell type. The only genes that are uniquely required for the response pathway in either mating type are those coding for the receptors. Either the a factor-receptor or the α factor-receptor interaction switches on the same response pathway. Mutations that eliminate steps in the common pathway have the same effects in both cell types (Bender and Sprague, 1986).




Figure 17.3 Either a or a factor/receptor interaction triggers the activation of a G protein, whose bg subunits transduce the signal to the next stage in the pathway.

The initial steps in the mating-type response are summarized in Figure 17.3. The components are similar to those of the "classical" receptor-G protein coupled systems (see 26 Signal transduction). The receptors are integral membrane proteins. (Ste2 is the α-receptor in the a cell; Ste3 is the a-receptor in the α cell.) When either receptor is activated, it interacts with the same G protein. The trimeric G protein consists of the subunits, α, β, and γ. The α subunit binds a guanine nucleotide. In the intact (trimeric) G protein, the α subunit carries GDP. When the pheromone receptor is activated, it causes the GDP to be displaced by GTP. As a result, the α subunit is released from the βγ dimer. This separation of subunits allows the G protein to activate the next protein in whatever pathway it is coupled to.


The most common mechanism used in such pathways is for the activated α subunit to interact with the target protein. However, the situation is different in the mating type pathway, where the βγ dimer activates the next stage in the pathway. The component proteins of the G-trimer are identified by mutations in three genes, SCG1, STE4, and STE18, that affect the response to binding pheromone. Inactivation of SCG1, which codes for the Gα protein, causes constitutive expression of the pheromone response pathway (because Gα is unable to maintain Gβγ in the inactive trimeric form). The mutation is lethal, because its effects include arrest of the cell cycle. Inactivation of STE4 (codes for Gβ) or of STE18 (codes for Gα) create sterility by abolishing the mating-type response (because the next step in the pathway cannot be activated; for review see Kurjan, 1992; Kurjan, 1993).




Figure 17.4 The same mating type response is triggered by interaction of either pheromone with its receptor. The signal is transmitted through a series of kinases to a transcription factor; there may be branches to some of the final functions.


Figure 26.29 Homologous proteins are found in signal transduction cascades in a wide variety of organisms.

The remaining STE genes identify later steps in the pathway. They form the cascade shown in Figure 17.4, in which the signal is passed from one to the next, ultimately activating the genes needed for mating. The genes whose products act at the beginning of the cascade code for kinases; kinases such as Ste11 and Ste7 phosphorylate the next protein in the series, thereby activating it. Eventually the transcription factor Ste12 is activated; it in turn activates genes whose products are needed for mating. (Analogous cascades are found in higher organisms, and are compared with the yeast cascade later, in Figure 26.29


There are several STE genes that have not yet been placed into the cascade, and the order of all the components is not yet certain. So genes such as FUS3 and KSS1, which code for kinases, may belong within the cascade or represent branches from it. The principle, however, is clear: the signal created by interaction of pheromone with receptor is passed along a cascade that culminates by repressing functions needed for the normal cell cycle, and by activating functions needed for mating.


Some of the end targets for the cascade are direct substrates for one of the kinases; for example, Fus3 kinase acts on Cln3, which is one of 3 Cln proteins needed for cell cycle progression. Other targets are controlled at the level of gene expression; for example, another of the Cln proteins, Cln2, is the target for action of the protein far1, whose expression is activated by the transcription factor Ste12.




Reviews
Kurjan, J. (1992). Pheromone response in yeast. Ann. Rev. Biochem 61, 1097-1129.
Kurjan, J. (1993). The pheromone response pathway in S. cerevisiae. Ann. Rev. Genet. 27, 147-179.
Nasmyth, K. (1982). Molecular genetics of yeast mating type. Ann. Rev. Genet. 16, 439-500.

Research
Bender, A. and Sprague, G. F., Jr. (1986). Yeast peptide pheromones, a-factor and alpha-factor, activate a common response mechanism in their target cells. Cell 47, 929-937.



Genes VII
Genes VII
ISBN: B000R0CSVM
EAN: N/A
Year: 2005
Pages: 382

flylib.com © 2008-2017.
If you may any questions please contact us: flylib@qtcs.net