Polarity establishment in many cells is thought to occur via positive feedback that reinforces even tiny asymmetries in polarity protein distribution. Cdc42 and related GTPases are activated and accumulate in a patch of the cortex that defines the front of the cell. Positive feedback enables spontaneous polarization triggered by stochastic fluctuations, but as such fluctuations can occur at multiple locations, how do cells ensure that they make only one front? In polarizing cells of the model yeast Saccharomyces cerevisiae, positive feedback can trigger growth of several Cdc42 clusters at the same time, but this multi-cluster stage rapidly evolves to a single-cluster state, which then promotes bud emergence. By manipulating polarity protein dynamics, we show that resolution of multi-cluster intermediates occurs through a greedy competition between clusters to recruit and retain polarity proteins from a shared intracellular pool.The cells of fungi and other eukaryotic organisms are generally asymmetric in shape and structure. This is possible because newly-formed cells can establish front and back ends that influence how each cell grows and develops. A protein called Cdc42 – which can cycle between an active and inactive form – establishes this cell “polarity”. The front of the cell is specified by the accumulation of active Cdc42 proteins in a small area of the membrane that surrounds the cell.However, it is not clear why the accumulation of active Cdc42 only happens in one place. Budding yeast is widely used as a model to study cell polarity. This yeast reproduces through the budding of new daughter cells out of one end of the mother cell. To achieve this, the mother establishes a single front end through the accumulation of active Cdc42. This marks the site where the daughter cell will emerge.Previous research has shown that during the early stages of cell polarization, Cdc42 clusters start to form at several places on the inner surface of the membrane. Only a single cluster emerges as the winner, while the others lose and shrink away. How does this happen? One possibility is that Cdc42 clusters all compete with each other to attract polarity proteins from the cell interior, so that when a protein falls off one cluster it can be picked up by another.Another possibility is that the winning cluster acquires a factor that stabilizes it, while the other clusters do not. Here, Wu et al. use microscopy and mathematical modelling to distinguish between these two possible scenarios in budding yeast. The experiments show that the speed of competition can be manipulated by altering how quickly key polarity proteins move between the membrane and the interior of the cell. Cells with slowed competition can maintain multiple fronts for long enough to make several buds at the same time.Wu et al.’s findings suggest that the formation of a single front in budding yeast is due to competition for polarity factors. The next challenge will be to understand how some cells in animals and other fungi manage to suppress this competition in order to produce more than one front.
Wu, C.-F., Chiou, J.-G., Minakova, M., Woods, B., Tsygankov, D., Zyla, T. R., … Lew, D. J. (2015). Role of competition between polarity sites in establishing a unique front. ELife, 4. https://doi.org/10.7554/elife.11611