Browsing by Author "Lew, Daniel"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Chemotactic movement of a polarity site enables yeast cells to find their mates.
    (Proceedings of the National Academy of Sciences of the United States of America, 2021-06) Ghose, Debraj; Jacobs, Katherine; Ramirez, Samuel; Elston, Timothy; Lew, Daniel
    How small eukaryotic cells can interpret dynamic, noisy, and spatially complex chemical gradients to orient growth or movement is poorly understood. We address this question using Saccharomyces cerevisiae, where cells orient polarity up pheromone gradients during mating. Initial orientation is often incorrect, but polarity sites then move around the cortex in a search for partners. We find that this movement is biased by local pheromone gradients across the polarity site: that is, movement of the polarity site is chemotactic. A bottom-up computational model recapitulates this biased movement. The model reveals how even though pheromone-bound receptors do not mimic the shape of external pheromone gradients, nonlinear and stochastic effects combine to generate effective gradient tracking. This mechanism for gradient tracking may be applicable to any cell that searches for a target in a complex chemical landscape.
  • Thumbnail Image
    ItemOpen Access
    Mechanistic insights into actin-driven polarity site movement in yeast.
    (Molecular biology of the cell, 2020-05) Ghose, Debraj; Lew, Daniel
    Directed cell growth or migration are critical for the development and function of many eukaryotic cells. These cells develop a dynamic "front" (also called "polarity site") that can change direction. Polarity establishment involves autocatalytic accumulation of polarity regulators, including the conserved Rho-family GTPase Cdc42, but the mechanisms underlying polarity reorientation remain poorly understood. The tractable model yeast, Saccharomyces cerevisiae, relocates its polarity site when searching for mating partners. Relocation requires polymerized actin, and is thought to involve actin-mediated vesicle traffic to the polarity site. In this study, we provide a quantitative characterization of spontaneous polarity site movement as a search process and use a mechanistic computational model that combines polarity protein biochemical interactions with vesicle trafficking to probe how various processes might affect polarity site movement. Our findings identify two previously documented features of yeast vesicle traffic as being particularly relevant to such movement: tight spatial focusing of exocytosis enhances the directional persistence of movement, and association of Cdc42-directed GTPase-Activating Proteins with secretory vesicles increases the distance moved. Furthermore, we suggest that variation in the rate of exocytosis beyond simple Poisson dynamics may be needed to fully account for the characteristics of polarity site movement in vivo.