[GAR]: A Novel Type of Prion Involved in Glucose Signaling and Environmental Sensing in S. cerevisiae

Several well-characterized fungal proteins act as prions, proteins capable of multiple conformations, each with different activities, at least one of which is selfpropagating. We report a protein-based heritable element that confers resistance to glucosamine, [GAR+]. Genetically it resembles other yeast prions: it appears spontaneously at a rate higher than mutations and is transmissible by non-Mendelian, cytoplasmic inheritance. However, [GAR+] is in other ways profoundly different from known prions. [GAR+] propagation involves Pmal, the plasma membrane protein pump, and [GAR+] formation is induced by Stdl, a member of the Snf3/Rgt2 glucose signaling pathway. Also, [GAR+] does not appear to involve the formation of an amyloid template and the prion state represents only a fraction of the Pmal protein in the cell,· consistent with the prion form constituting a complex between Pmal and Stdl, a much lower abundance protein. [GAR+] propagation is subject to a strong species barrier, as substitution of PMAl from other Saccharomyces species blocks propagation to s.. cerevisiae PMAl. Direct competition between [gar-] and [GAR+] cells indicate that cells carrying [GAR+] have an advantage under certain environmental conditions. [GAR+] appears spontaneously in a yeast isolated from a variety of sources and can be induced by co-culturing yeast and a number ofStaphylococcus species. Overall, [GAR+] expands the conceptual framework for self-propagating protein-based elements of inheritance to include non-amyloid, potentially multicomponent systems such as transmembrane proteins and signal transducers.