Abstract

Co-authors: Brian Drawert (UC Santa Barbara), Michael Lawson (Uppsala University), Tau-Mu Yi (UC Santa Barbara), Mustafa Khammash (ETH Zurich), Otger Campas (UC Santa Barbara), Michael Trogdon (UC Santa Barbara) AbstractPolarization is an essential behavior of living cells, yet the dynamics of this symmetry-breaking process are not fully understood. Previously, noise was thought to interfere with this process; however, we show that stochastic dynamics plan an essential role in robust cell polarization and the dynamic response to changing cues. 

To further our understanding of polarization, we have developed a spatial stochastic model of cellular polarization during mating of Saccharomyces cerevisiae. Specifically we investigate the ability of yeast cells to sense a spatial gradient of mating pheromone and respond by forming a projection in the direction of the mating partner. Our mechanistic model integrates three components of the polarization process: the G-protein cycle activated by pheromone bound receptors, the focusing of a Cdc42 polarization cap, and the formation of the tight localization of proteins on the membrane known as the polarisome. 

Our results demonstrate that higher levels of stochastic noise result in increased robustness, giving support to a cellular model where noise and spatial heterogeneity combine to achieve robust biological function. Additionally, our simulations predict that two positive feedback loops are required to generate the spatial amplification to produce focal polarization. We combined our modeling with experiments to explore the critical role of the polarisome scaffold protein Spa2 during yeast mating, and as a result, have characterized a novel positive feedback loop critical to focal polarization via the stabilization of actin cables.