A Predictive Model for Yeast Cell Polarization in Pheromone Gradients
Fig 1
Basics of yeast mating and model.
A) Mating as a developmental switch. Exposing haploid cells to pheromone makes them exit the cell division cycle, polarize towards, and fuse with a cell of the opposite mating type to form a diploid cell. Cells recover and resume budding if the pheromone signal disappears. The polarisome protein, Spa2 (shown in green and red), concentrates at the incipient bud site, at the bud tip as cells grow, at the bud neck during cytokinesis, and at the shmoo tip and fusion site during mating. We use the rate of accumulation of a fluorescent protein expressed from the FUS1 promoter, a gene induced by pheromone stimulation, as a readout of pheromone-induced signaling. B) The pheromone response pathway of a cells. α-factor diffuses through the cell wall and binds to the α-factor receptor (Ste2, a G protein-coupled receptor (GPCR)), which activates a trimeric G protein. The G protein recruits and activates two scaffolding proteins. One (Far1) recruits the actin polymerization machinery that leads to cell polarization and activates the kinase that activates the MAP kinase cascade. The other (Ste5) is responsible for the assembly of a MAP kinase cascade that activates the MAP kinase Fus3, leading to the induction of mating genes. Once phosphorylated by Fus3, Far1 arrests the cell cycle in G1. C) A two-dimensional model of cell polarization. The left panel shows a cell, the right a more detailed view introducing the various parameters in the model. Actin is polymerized into short filaments, that interact with each other and these are bundled together to form actin cables that cross the cell. The nucleation of filaments is proportional to both the local density of Cdc42 and to the concentration of pheromone. The endocytosis of markers at the membrane is described by very simple attachment/detachment dynamics (kon and koff) and their diffusion in the plane of the membrane is described by a diffusion constant, Dm, while their diffusion in the cytoplasm is described by a separate constant, Db. D) According to the fact that a polarisome occupies approximately 10% of the total membrane length, [12], we divide the membrane into 10 subregions (sectors). At each time point, κ(t,.), the parameter that describes the dynamics of the pheromone receptor, has a constant value within one segment. E) The temporal evolution of the effective pheromone receptor activity κ is ruled by an Ornstein-Uhlenbeck process. The parameter λ is the the noise damping. The parameter σ is the standard deviation of the instantaneous change of κ(t).