Fungal mating pheromones: choreographing the dating game

Abstract

Pheromones are ubiquitous from bacteria to mammals - a testament to their importance in regulating inter-cellular communication. In fungal species, they play a critical role in choreographing interactions between mating partners during the program of sexual reproduction. Here, we describe how fungal pheromones are synthesized, their interactions with G protein-coupled receptors, and the signals propagated by this interaction, using Saccharomyces cerevisiae as a reference point. Divergence from this model system is compared amongst the ascomycetes and basidiomycetes, which reveals the wealth of information that has been gleaned from studying pheromone-driven processes across a wide spectrum of the fungal kingdom.

Figure 1. Processing of S. cerevisiae a and α mating pheromones

A). Processing of α factor: The secretion signal (blue) is cleaved to produce the α propheromone, which is glycosylated in the endoplasmic reticulum. Upon transport to the golgi apparatus, three proteolytic steps remove the proregion (green) and connecting regions (yellow) that separate copies of mature α factor (pink). B) Processing of a factor: In the cytosol, a propheromone is farnesylated at a conserved cysteine in the C-terminal CAAX motif (C = cysteine, A = aliphatic, X= any). The amino acids (yellow) proceeding the cysteine are then removed and replaced with a carboxymethyl group. Finally, two proteolytic events remove N-terminus amino acids (green) to produce the mature a factor (pink).

Figure 2. Dikarya phylogenetic tree

The dikarya sub-kingdom includes the Ascomycota and Basidiomycota phyla. Only species discussed in the text are included here; genera Sordaria → Magnaporthe are within the Sordariomycete class. Tree is not drawn to scale.

Figure 3. The S. cerevisiae Ste2 pheromone receptor

In S. cerevisiae, the G-protein coupled receptor Ste2 recognizes α factor via extracellular (EC) loops 2 and 3 and transmembrane domains 1, 5 and 6 (shown in pink). Ste2 associates with G-proteins and activates downstream signaling primarily via the C-terminal tail and intracellular (IC) loop 3. The IC2 region is not shown.

Figure 4. The mating MAPK signaling cascade

Following activation of the pheromone receptor in S. cerevisiae, the associated G-protein α subunit exchanges GDP with GTP, releasing β and γ subunits. The βγ complex then interacts with both the Ste5 scaffold and Ste20, which causes sequential activation of kinases Ste11, Ste7 and Fus3. Finally, Fus3 enters the nucleus where it regulates the transcription factor Ste12 to regulate expression of genes important for mating. The Kss1 kinase is primarily involved in filamentation signaling but can also substitute for Fus3 in mating signaling.