User:Ilya/Yeast/Mating pheromone response pathway/Pheromone

The Saccharomyces cerevisiae mating pheromone a-factor is a prenylated and carboxyl methylated extracellular peptide signaling molecule.

Like the peptide hormones secreted by higher eukaryotes, the yeast mating pheromones are initially synthesized as larger precursors that undergo posttranslational modification and proteolytic processing before their export from the cell. Despite their functional equivalence as signaling molecules, the a-factor and alpha-factor pheromones are structurally quite dissimilar and exemplify distinct paradigms for biogenesis.

The maturation of alpha-factor is well characterized and involves the classical  secretory pathway (ER -> Golgi -> secretory vesicles). Subsequent to its translocation across the ER membrane, the alpha-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 to our extensive understanding of alpha-factor maturation, our view of the events involved in a-factor biogenesis is still incomplete.

An important difference between the two pheromones is that secretion of a-factor is mediated by a nonclassical export mechanism.

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 COOH-terminal maturation of the a-factor precursor is directed by its CAAX sequence. The a-factor precursor can be subdivided into three functional segments: (a) the mature portion, which is ultimately secreted; (b) the NH2-terminal extension; (c) the COOH-terminal CAAX motif.

Biogenesis of a-factor occurs by an ordered series of events involving first COOH-terminal CAAX modification, then NH2-terminal processing, and finally export from the cell (He et al., 1991; Michaelis, 1993; Sapperstein et al., 1994).

In mutants (ram1, ram2, and ste14) defective in CAAX modification, biologically active a-factor is not produced.

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