Yeast Dynamically Modify Their Environment to Achieve Better Mating Efficiency

Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Science Signaling (Impact Factor: 6.28). 08/2011; 4(186):ra54. DOI: 10.1126/scisignal.2001763
Source: PubMed


The maintenance and detection of signaling gradients are critical for proper development and cell migration. In single-cell organisms, gradient detection allows cells to orient toward a distant mating partner or nutrient source. Budding yeast expand their growth toward mating pheromone gradients through a process known as chemotropic growth. MATα cells secrete α-factor pheromone that stimulates chemotropism and mating differentiation in MATa cells and vice versa. Paradoxically, MATa cells secrete Bar1, a protease that degrades α-factor and that attenuates the mating response, yet is also required for efficient mating. We observed that MATa cells avoid each other during chemotropic growth. To explore this behavior, we developed a computational platform to simulate chemotropic growth. Our simulations indicated that the release of Bar1 enabled individual MATa cells to act as α-factor sinks. The simulations suggested that the resultant local reshaping of pheromone concentration created gradients that were directed away from neighboring MATa cells (self-avoidance) and that were increasingly amplified toward partners of the opposite sex during elongation. The behavior of Bar1-deficient cells in gradient chambers and mating assays supported these predictions from the simulations. Thus, budding yeast dynamically remodel their environment to ensure productive responses to an external stimulus and avoid nonproductive cell-cell interactions.

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Available from: Henrik G Dohlman, Jun 27, 2014
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    • "Recent advances in live-cell imaging and computational image analysis have generated new insights into many aspects of cell signaling. In yeast, these new tools have been combined with mathematical modeling to investigate dose alignment (Yu et al., 2008), noise regulation (Dixit et al., 2014), cell fate decisions (Doncic et al., 2011) and gradient sensing (Hao et al., 2008; Jin et al., 2011; Howell et al., 2012; Dyer et al., 2013; Kelley et al., 2015). The success of these investigations motivated us to apply a similar approach to investigate Sst2's role in regulating receptor endocytosis. "
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    ABSTRACT: G-protein coupled receptor (GPCR) signaling is fundamental to physiological processes, such as vision, the immune response and wound healing. In the budding yeast Saccharomyces cerevisiae, GPCRs detect and respond to gradients of pheromone during mating. Following pheromone stimulation, the GPCR Ste2 is removed from the cell membrane and new receptors are delivered to the growing edge. The Regulator of G-protein Signaling (RGS) protein, Sst2, acts by accelerating GTP hydrolysis and facilitating pathway desensitization. Sst2 is also known to interact with the receptor Ste2. Here we show that Sst2 is required for proper receptor recovery at the growing edge of pheromone-stimulated cells. Mathematical modeling suggested pheromone-induced synthesis of Sst2 and its interaction with the receptor function together to reestablish a receptor pool at the site of polarized growth. To validate the model we used targeted genetic perturbations to selectively disrupt key properties of Sst2 and disrupt its induction by pheromone. Together, our results reveal that a regulator of G protein signaling can also regulate the G protein-coupled receptor. Whereas Sst2 negatively regulates G protein signaling, it acts in a positive manner to promote receptor retention at the growing edge.
    Molecular biology of the cell 08/2015; DOI:10.1091/mbc.E14-12-1635 · 4.47 Impact Factor
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    • "Adaptation mechanisms target the pheromone response pathway at many levels. First, MATa cells secrete the protease Bar1 to degrade a factor, lower its concentration in the medium, and sharpen the local pheromone gradient toward the nearest mating partner (Jin et al., 2011; Sprague and Herskowitz, 1981). Second, the regulator of G-protein-signaling protein, Sst2, attenuates signaling through interactions with both the receptor and the guanosine triphosphate-bound Ga protein (Dohlman , 2009). "
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    ABSTRACT: Cellular behavior is frequently influenced by the cell's history, indicating that single cells may memorize past events. We report that budding yeast permanently escape pheromone-induced cell-cycle arrest when experiencing a deceptive mating attempt, i.e., not reaching their putative partner within reasonable time. This acquired behavior depends on super-assembly and inactivation of the G1/S inhibitor Whi3, which liberates the G1 cyclin Cln3 from translational inhibition. Super-assembly of Whi3 is a slow response to pheromone, driven by polyQ and polyN domains, counteracted by Hsp70, and stable over generations. Unlike prion aggregates, Whi3 super-assemblies are not inherited mitotically but segregate to the mother cell. We propose that such polyQ- and polyN-based elements, termed here mnemons, act as cellular memory devices to encode previous environmental conditions.
    Cell 12/2013; 155(6):1244-57. DOI:10.1016/j.cell.2013.10.046 · 32.24 Impact Factor
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    • "In addition to producing pheromones, yeast cells also produce proteases that cleave and inactivate pheromones, thus actively remodelling the pheromone landscape in their environment. In particular, the alpha-factor protease Bar1, which is released by MATa cells, helps these cells avoid each other [32,33]. Simplified setups, such as release of pheromone through micropipette or microfluidic devices, have been used to show that MATa cells orient growth towards the source of an artificial pheromone gradient [34–37]. "
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    ABSTRACT: Many cells are able to orient themselves in a non-uniform environment by responding to localized cues. This leads to a polarized cellular response, where the cell can either grow or move towards the cue source. Fungal haploid cells secrete pheromones to signal mating, and respond by growing a mating projection towards a potential mate. Upon contact of the two partner cells, these fuse to form a diploid zygote. In this review, we present our current knowledge on the processes of mating signalling, pheromone-dependent polarized growth and cell fusion in Saccharomyces cerevisiae and Schizosaccharomyces pombe, two highly divergent ascomycete yeast models. While the global architecture of the mating response is very similar between these two species, they differ significantly both in their mating physiologies and in the molecular connections between pheromone perception and downstream responses. The use of both yeast models helps enlighten both conserved solutions and species-specific adaptations to a general biological problem.
    Open Biology 03/2013; 3(3):130008. DOI:10.1098/rsob.130008 · 5.78 Impact Factor
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