Browsing by Subject "Gradient sensing"
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Item Open Access How Yeast Cells Find Their Mates(2019) Henderson, Nicholas TrubianoExtracellular chemical gradients provide signals that guide a broad spectrum of different cellular processes. By accurately sensing and responding to chemical gradients, immune cells can chase down invading pathogens, sperm cells can locate a distant egg, and growing axons can form connections in the developing nervous system. Haploid cells of the budding yeast Saccharomyces cerevisiae grow up gradients of pheromone in order to locate and fuse with nearby mating partners. Gradient sensing should be challenging for yeast, because they must detect a minute difference in concentration across their small cell bodies. Nevertheless, yeast cells can orient with remarkable accuracy in shallow pheromone gradients. Several mechanisms have been proposed to explain how yeast cells locate their partners, but it remains unclear whether, and to what degree each of the proposed mechanisms contributes.
We imaged fluorescent polarity probes in real time during mating events and found that cells located their partners in a multi-step process. First, cells placed a weak cluster of polarity proteins in approximately the correct location, despite a previously unappreciated challenge posed by asymmetrically distributed pheromone receptors. Cells were able to overcome receptor asymmetry by sensing the ratio, rather than the number, of active pheromone receptors. Second, the polarity cluster proceeded to move erratically around the cortex during an “indecisive phase.” We found evidence that cells switched to a local sensing mechanism during the indecisive phase, wherein cells used the mobile polarity cluster like a nose to search for areas where the local pheromone concentration was high. Third, the polarity cluster stabilized adjacent to a partner cell’s cluster and remained stationary until the partners met in the middle and fused.
Item Open Access Mechanisms of Chemotropism in Fungi: Saccharomyces cerevisiae as a Model(2021) Clark-Cotton, Manuella RossetteBudding yeast decode pheromone gradients to locate mating partners, providing a model of chemotropism in fungi. How yeast polarize toward a single partner in crowded environments is unclear. Initially, cells often polarize in unproductive directions, but then they relocate the polarity site until two partners’ polarity sites align, whereupon the cells “commit” to each other by stabilizing polarity to promote fusion. Using live-cell fluorescence microscopy, computational modeling, and quantitative autocorrelation analyses, I address the role of the early mobile polarity sites, finding that commitment by either partner failed if just one partner was defective in generating, orienting, or stabilizing its mobile polarity sites. Mobile polarity sites were enriched for pheromone receptors and G proteins, suggesting that such sites engage in an exploratory search of the local pheromone landscape, stabilizing only when they detect elevated pheromone levels. Mobile polarity sites were also enriched for pheromone secretion factors, and simulations suggest that only focal secretion at polarity sites would produce high pheromone concentrations at the partner’s polarity site, triggering commitment.
Item Open Access Mechanisms of Gradient Tracking During Yeast Mating(2012) Johnson, Jayme MMany cells are remarkably proficient at tracking even shallow chemical gradients, despite tiny differences in receptor occupancy across the cell. Stochastic receptor-ligand interactions introduce considerable noise in instantaneous receptor occupancy, so it is thought that spatial information must be integrated over time to allow noise filtering. The mechanism of temporal integration is unknown. We used the mating response of the budding yeast, Saccharomyces cerevisiae, as a model to study eukaryotic gradient tracking.
During mating, yeast cells polarize and grow up a gradient of pheromone to find and fuse with opposite-sex partners. Exposure to pheromone causes polarity regulators to cluster into a tight "patch" at the cortex, directing growth toward that site. Timelapse microscopy of fluorescently-labeled polarity proteins revealed that the patch wandered around the cortex during gradient tracking. Mathematical modeling and genetic analysis suggested that fusion of vesicles near the polarization site could perturb the polarity patch and promote wandering. Wandering is decreased due to global effects from pheromone signaling as well as interactions between receptor-activated Gβ and the exchange factor for the polarity regulator Cdc42. We found that artificially stabilizing patch wandering impaired accurate gradient tracking.
We suggest that ongoing polarized vesicle traffic causes patch wandering, which is locally reduced by pheromone-bound receptors. Thus, over time, spatial information from the pheromone gradient biases the random wandering of the polarity patch so that growth occurs predominantly up-gradient. Such temporal integration may enable sorting the low signal from stochastic noise when tracking shallow gradients.