Title: Courtship is a Two-Way Conversation: Yeast Mating as a Model of Cell-Cell Communication

Abstract: Many cells track chemical signals, but mechanisms of target location are elusive. The budding yeast, an established model of cell-cell communication, tracks a pheromone signal during mating. Pheromone binds to cell surface receptors, triggering the concentration of polarity proteins into a “polarity patch” at a small zone of the cell cortex. The patch is oriented toward the partner and, through its effectors, directs polarized growth toward the mate. In classical models, a cell first decodes the pheromone gradient and then polarizes toward the region of highest signal. However, yeast in artificial gradients can improve their orientation by moving the patch, in a process perhaps mediated by local pheromone sensing and secretion. Therefore, an alternative “exploratory polarization” paradigm posits that mobile polarity sites search the cortex, stopping when the patches of two partner cells are aligned and each cell senses a high local pheromone signal. Cells in mating mixes exhibit an initial “indecisive” period with weak and erratically mobile polarity clusters instead of a strong polarity patch, before making a strong patch oriented towards the partner (“commitment”). We asked whether these early clusters mediated exploratory polarization or if the cells performed a global survey of the pheromone landscape. Strikingly, imaging of mating mixes revealed that wildtype cells did not commit to various mutants with impaired clustering, instead displaying extended indecisive behavior. These findings suggest that local signaling at mobile clusters is key to commitment. Sensing and secretion markers were enriched at transient polarity clusters, providing further support for the exploratory polarization model.