Friday, September 4, 2009

Mating Factors

Definition
Mating factors are a family of pheromones that were initially discovered in Saccharomyces cerevisiae, necessary for fungal conjugation. The alpha-factor pheromone induces conjugation in yeast by binding to Ste2p protein.

Discovery
In Saccharomyces cerevisiae, the peptide mating pheromones a-factor and a-factor function to promote conjugation between cells of the opposite mating type, MATa and MATa. Manney et al described the mutants of Saccharomyces cerevisiae with an altered response to mating factor (either more resistant or more sensitive) that permitted a genetic dissection of the pathway of hormone action. One such class of mutants, the a factor resistant mutants, has been isolated and found to be sterile (nonmating), implying that the ability to respond to a factor is essential for mating1,2. The maturation of a-factor is well characterized and involves the "classical" secretory pathway. Subsequent to its translocation across the endoplasmic reticulum membrane, the a-factor precursor undergoes signal sequence cleavage, glycosylation, a series of proteolytic processing steps in the lumenal compartments of the secretory pathway, and then exits the cell via exocytosis. In contrast a-factor biogenesis is mediated by a "nonclassical" export mechanism3.

Structural Characteristics
Mature bioactive a-factor is a prenylated and methylated dodecapeptide, derived by the posttranslational maturation of a precursor encoded by the similar and functionally redundant genes MFA1 and MFA2. The a-factor precursor can be subdivided into three functional segments: (a) the mature portion, which is ultimately secreted; (b) the NH2-terminal extension; and (c) the COOH-terminal CAAX motif (C is cysteine, A is aliphatic, and X is one of many residues). Biogenesis of mating factor occurs by an ordered series of events involving first COOH-terminal CAAX modification, then NH2-terminal processing, and finally export from the cell4,5.

Mode of Action
Mating factor binds and activates specific cell surface receptors, thereby inducing behavioral or physiological responses in the responding organism or cell that leads to the transfer or union of genetic material between organisms or cells. MATa cells make a linear tridecapeptide, called a factor that arrests MATa cells in the G1 phase of the cell cycle; MATa cells make a decapeptide, called a factor, which has similar effects on MATa cells. The a and a factor pheromones apparently prepare cells for mating by inducing agglutination between the two cell types and by synchronizing their cell cycles 6.The mating pheromone can either be retained on the cell surface or secreted. A signal transduction process resulting in the relay, amplification or dampening of a signal generated in response to pheromone exposure in organisms that undergo conjugation with cellular fusion.

Response to pheromone elicits arrest in the G1 phase of the cell cycle, cell wall changes, morphological alterations, and induction of genes that encode products involved in aspects of mating or pheromone response. Mutants defective in pheromone production or response are sterile7. Addition of exogenous a-factor can partially alleviate these mating defects under certain conditions.

Functions
In Saccharomyces cerevisiae, mating type and the ability to sporulate are controlled by two alternative alleles of the mating-type locus MAT. Cells that express either the MATa or the MATa allele, regardless of ploidy or dosage, can mate with cells that express the alternative allele. Cells that are heterozygous at this locus can sporulate. Normally, mating and sporulation are mutually exclusive. Although mating and sporulation are determined by this single locus, these phenotypes involve the expression of many specific and nonspecific functions coded by genes that are not linked to the mating-type locus. Consequently, the MAT locus appears to regulate the expression of the structural genes that are necessary for mating and sporulation.

MATa is complex codes for a MATa1 and MATa2, MATa1 functions as a positive regulator of a-specific functions, such as secretion of the mating pheromone, a-factor, synthesis of the a-specific surface agglutinin, and the ability to respond to the a-specific pheromone, a-factor. MATa2 acts as a negative regulator of a- specific functions, such as secretion of a-factor, synthesis of the barrier activity (which inactivates a-factor), synthesis of the a-specific surface agglutinin, and as a positive regulator of sporulation 8.

References
1.Hartwell LH (1980). Mutants of Saccharomyces cerevisiae unresponsive to cell division control by polypeptide mating hormones. J. Cell Biol., 85(3):811-822.
2.Manney TR, Woods V (1976). Mutants of Saccharomyces cerevisiae resistant to the a- mating-type factor. Genetics., 82(4):639-644.
3.Kuchler K, Sterne RE, Thorner J (1989). Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. EMBO., 8(13):3973-3984.
4.Michaelis S, Herskowitz I (1988). The a-factor pheromone of Saccharomyces cerevisiae is essential for mating. Mol. Cell. Biol., 8:1309-1318.
5.Sapperstein S, Berkower C, Michaelis S (1994). Nucleotide sequence of the yeast STE14 gene, which encodes farnesylcysteine carboxyl methyltransferase, and demonstration of its essential role in a-factor export. Mol. Cell. Bio., 14:1438-1449.
6.Book : Sexual Interactions in Eukaryotic Microbes. Chapter: The Isolation, Characterization, and Physiological Effects of the Saccharomyces cerevisiae Sex Pheromones., 21-51. By Manney TR, Duntzer W, Betz R
7.Cross F, Hartwell LH, Jackson C, Konopka JB (1988). Corljugation in Saccharomyces cerevisiae. Annu. Rev. Cell Biol., 4:430-457.
8.Manney TR, Jackson P, Meade J (1983). Two Temperature-sensitive Mutants of Saccharomyces cerevisiae with Altered Expression of Mating-Type Functions. The journal of cell biology., 96:1592-1600.

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