A heritable switch in carbon source utilization driven by an unusual yeast prion.
Several well-characterized fungal proteins act as prions, proteins capable of multiple conformations, each with different activities, at least one of which is self-propagating. Through such self-propagating changes in function, yeast prions act as protein-based elements of phenotypic inheritance. We report a prion that makes cells resistant to the glucose-associated repression of alternative carbon sources, [GAR(+)] (for "resistant to glucose-associated repression," with capital letters indicating dominance and brackets indicating its non-Mendelian character). [GAR(+)] appears spontaneously at a high rate and is transmissible by non-Mendelian, cytoplasmic inheritance. Several lines of evidence suggest that the prion state involves a complex between a small fraction of the cellular complement of Pma1, the major plasma membrane proton pump, and Std1, a much lower-abundance protein that participates in glucose signaling. The Pma1 proteins from closely related Saccharomyces species are also associated with the appearance of [GAR(+)]. This allowed us to confirm the relationship between Pma1, Std1, and [GAR(+)] by establishing that these proteins can create a transmission barrier for prion propagation and induction in Saccharomyces cerevisiae. The fact that yeast cells employ a prion-based mechanism for heritably switching between distinct carbon source utilization strategies, and employ the plasma membrane proton pump to do so, expands the biological framework in which self-propagating protein-based elements of inheritance operate.
Brown
Jessica C S
JC
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Lindquist
Susan
S
D002244:Carbon / Q000378:metabolism*; D015870:Gene Expression; D005800:Genes, Fungal / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010641:Phenotype; D011328:Prions; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D009004:Monosaccharide Transport Proteins; D011328:Prions; C112512:RGT2 protein, S cerevisiae; C104463:SNF3 protein, S cerevisiae; C081335:STD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002244:Carbon; C092477:PMA1 protein, S cerevisiae; D006180:Proton-Translocating ATPases; D005947:Glucose