Mechanism of commitment to a mating partner in Saccharomyces cerevisiae

Abstract

Many cells detect and follow gradients of chemical signals to perform their functions. Yeast cells use gradients of extracellular pheromones to locate mating partners, providing a tractable model to understand how cells decode the spatial information in gradients. To mate, yeast cells must orient polarity toward the mating partner. Polarity sites are mobile, exploring the cell cortex until they reach the proper position, where they stop moving and “commit” to the partner. A simple model to explain commitment posits that a high concentration of pheromone is only detected upon alignment of partner cells’ polarity sites, and causes polarity site movement to stop. Here we explore how yeast cells respond to partners that make different amounts of pheromone. Commitment was surprisingly robust to varying pheromone levels, ruling out the simple model. We also tested whether adaptive pathways were responsible for the robustness of commitment, but our results show that cells lacking those pathways were still able to accommodate changes in pheromone. To explain this robustness, we suggest that the steep pheromone gradients near each mating partner's polarity site trap the polarity site in place.

Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating

“…Remarkably, in this case all simulations produced a stable polarity site located in the region of high pheromone within 30 min ( Fig 6B and S8 Movie ). These results are consistent with experimental findings in which cells secreting only 20% of the amount of pheromone as wildtype cells are able to stabilize the polarity sites of mating partners [ 53 ]. Polarity stabilization occurred more rapidly in 0–1.2 nM than in 1.5–5.8 nM gradients ( Fig 6C ), consistent with the idea that the main obstacle to polarity stabilization is provided by competition with distinct polarity clusters seeded by the background levels of pheromone.…”

“…In turn, higher Cdc42 activity leads to an increase in the local concentration of receptors, reinforcing Cdc42 activity and promoting the formation of a stable polarity site. Interestingly, this mechanism of gradient tracking is able to respond effectively to pheromone gradients of low peak concentration (1.2 nM), consistent with observations that cells in which pheromone production has been reduced by 80% are still able to successfully signal their location to mating partners [53]. A potential limitation of this mechanism for gradient tracking is that cells can be confused when the gradient is superimposed on a background of constant pheromone (e.g., the case in which the gradient ranges from 1.5-5.8 nM).…”

“…With this number, the maximum pheromone concentration that the partner cell is exposed to is likely to be below 10 nM [ 19 ]. Surprisingly, yeast cells secreting only 20% as much pheromone (peak concentration around 1–2 nM) are still able to stabilize their mating partner’s polarity site [ 53 ]. This is well below the concentration of uniform pheromone required for stabilization of a polarity site [ 51 , 54 ].…”

“…This is well below the concentration of uniform pheromone required for stabilization of a polarity site [ 51 , 54 ]. These findings suggested it may be the pheromone gradient, rather than the absolute pheromone concentration, that stabilizes the position of the polarity site [ 53 ]. To test the plausibility of this hypothesis, we included pheromone molecules in our combined polarity circuit simulations ( Fig 5A and Table 3 ).…”

Comparative Proteomic Analysis of Two Commonly Used Laboratory Yeast Strains: W303 and BY4742

“…To become diploid, yeast cells of mating type a ( MATa ) secrete a specific molecule, mating factor a, which attracts them to the cells of mating type alpha ( MATα ) and vice versa. The mating type factors bind specific receptors on the membrane of the opposite mating type cells [ 23 ]. Usually, the mating type of research laboratory yeast strains is known, but in some cases, the mating type must be determined (such as after tetrad dissections) or confirmed (such as after purchasing the strain from a commercial vendor or when receiving it as a gift from another laboratory).…”