Symmetry Breaking in the Life Cycle of the Budding Yeast

The budding yeast Saccharomyces cerevisiae has been an invaluable model system for the study of the establishment of cellular asymmetry and growth polarity in response to specific physiological cues. A large body of experimental observations has shown that yeast cells are able to break symmetry and establish polarity through two coupled and partially redundant intrinsic mechanisms, even in the absence of any pre-existing external asymmetry. One of these mechanisms is dependent upon interplay between the actin cytoskeleton and the Rho family GTPase Cdc42, whereas the other relies on a Cdc42 GTPase signaling network. Integral to these mechanisms appear to be positive feedback loops capable of amplifying small and stochastic asymmetries. Spatial cues, such as bud scars and pheromone gradients, orient cell polarity by modulating the regulation of the Cdc42 GTPase cycle, thereby biasing the site of asymmetry amplification.The budding yeast Saccharomyces cerevisiae is a gift of nature, not just for its superb ability in fermentation to provide us food for hunger and pastime, but also for its relatively simple physiology, which has illuminated our understanding of many fundamental cellular processes. In particular, asymmetry is a way of life for the budding yeast, both when it grows vegetatively and initiates sexual reproductive cycles; as such, yeast has been an invaluable model for studying the establishment of cellular asymmetry. A haploid yeast cell in the G1 phase, which is round and grows isotropically, faces two options: to enter the mitotic cell cycle and grow a bud, or to refrain from cell cycle entry and form a mating projection (shmoo) toward a cell of the opposite mating type. In either case, the cell has to break symmetry to switch from isotropic growth to growth along a polarized axis (Fig. 1). These processes of cell polarity establishment are triggered either by internal signals from the cell cycle engine (budding) or by an external signal in the form of a pheromone gradient (mating).Open in a separate windowFigure 1.Symmetry breaking processes in the life cycle of budding yeast. Shown are the locations of actin patches, actin cables, and Cdc42 during polarized growth for both cycling cells and cells undergoing pheromone response. In G1 cells, Cdc42 is distributed symmetrically, and the actin cytoskeleton is not polarized. In response to cell cycle signals or mating pheromone stimulation, Cdc42 and the actin cytoskeleton become polarized: Cdc42 forms a “polar cap” and actin cables become oriented to allow for targeted secretion. Polarized growth further leads to formation of a bud (cell cycle signal) or formation of a mating projection (pheromone signal). Images represent GFP-Cdc42 (green), and rhodamine-phalloidin staining of filamentous actin (red).Pioneering work involving isolation and characterization of mutants deficient in various aspects of budding and shmoo formation identified key components of the molecular pathways underlying yeast polarized morphogenesis. Despite the relative simplicity of yeast, it has become increasingly clear that many of the genes that control the establishment of cell polarity are conserved between yeast and more complex eukaryotic organisms (see McCaffrey and Macara 2009; Munro and Bowerman 2009; Wang 2009; Nelson 2009). In particular, the small GTPase Cdc42, first discovered in yeast (Adams et al. 1990) and subsequently shown to be required for cell polarization in many eukaryotic organisms (Etienne-Manneville 2004), is the central regulator of yeast polarity.Common principles have begun to emerge to explain symmetry breaking under varying physiological conditions. One of these principles is the self-organizing nature of cell polarity. Whereas under physiological conditions yeast cells polarize toward an environmental asymmetry (pheromone gradient) or a “landmark,” i.e., the bud scar, deposited on the cell surface from a previous division (in a process called bud site selection), it is clear that the ability to undergo symmetry breaking to establish polarity in a random orientation is independent of these cues. It is tempting to speculate that the basic molecular machinery for symmetry breaking, which is required for asexual proliferation through budding, might have evolved independently of the machinery underlying mating and bud site selection.As in all polarized cell systems, yeast polarity is manifested as both an asymmetry in the distribution of signaling molecules and in the organization of the cytoskeleton. In yeast, the switch from an isotropic distribution of Cdc42 on the plasma membrane to a polarized distribution (Fig. 1) is required for the polarized organization of the actin cytoskeleton and membrane trafficking systems, and eventually orientated cell growth. Recent work also showed that the cytoskeleton and the membrane trafficking system can in turn impact the localization of Cdc42 and possibly other membrane‐associated regulatory molecules (Karpova et al. 2000; Wedlich-Soldner et al. 2004; Irazoqui et al. 2005; Zajac et al. 2005). A combination of experimental and theoretical analyses strongly suggests that the interplay between signaling and structural pathways is at the heart of the cell’s intrinsic ability to break symmetry.As there have been recent review articles on the polarized organization of budding yeast growth systems (Bretscher 2003; Pruyne et al. 2004b) and on the molecular parts list involved in cell polarization (Park and Bi 2007), this article is specifically focused on the mechanisms of symmetry breaking at two levels: first as a self-organization process accomplished through dynamic interplay between intrinsic signaling and cytoskeletal systems, which enables vegetative proliferation through bud formation; and second, as an adaptive process where polarity is spatially harnessed by physical cues that arise during bud-site selection and mating. Finally, we briefly extend our discussion to include the role of polarity in yeast aging and cell fate determination. This exciting, relatively new area of research has made important advances in our understanding of how asymmetry can be an important mechanism to ensure long-lasting fitness of a fast proliferating population.