Hsp90 Regulates Nongenetic Variation in Response to Environmental Stress

Summary Nongenetic cell-to-cell variability often plays an important role for the survival of a clonal population in the face of fluctuating environments. However, the underlying mechanisms regulating such nongenetic heterogeneity remain elusive in most organisms. We report here that a clonal yeast population exhibits morphological heterogeneity when the level of Hsp90, a molecular chaperone, is reduced. The morphological heterogeneity is driven by the dosage of Cdc28 and Cla4, a key regulator of septin formation. Low Hsp90 levels reduce Cla4 protein stability and cause a subpopulation of cells to switch to a filamentous form that has been previously suggested to be beneficial under certain hostile environments. Moreover, Hsp90-dependent morphological heterogeneity can be induced by environmental stress and is conserved across diverse yeast species. Our results suggest that Hsp90 provides an evolutionarily conserved mechanism that links environmental stress to the induction of morphological diversity.