Mutations gef1, stp22, STP26, and STP27 in Saccharomyces cerevisiae were identified as suppressors of the temperature-sensitive α-factor receptor (mutation ste2-3) and arginine permease (mutationcan1ts ). These suppressors inhibited the elimination of misfolded receptors (synthesized at 34°C) as well as damaged surface receptors (shifted from 22 to 34°C). Thestp22 mutation (allelic to vps23 [M. Babst and S. Emr, personal communication] and the STP26mutation also caused missorting of carboxypeptidase Y, andste2-3 was suppressed by mutations vps1,vps8, vps10, and vps28 but not by mutation vps3. In the stp22 mutant, both the mutant and the wild-type receptors (tagged with green fluorescent protein [GFP]) accumulated within an endosome-like compartment and were excluded from the vacuole. GFP-tagged Stp22p also accumulated in this compartment. Upon reaching the vacuole, cytoplasmic domains of both mutant and wild-type receptors appeared within the vacuolar lumen. Stp22p and Gef1p are similar to tumor susceptibility protein TSG101 and voltage-gated chloride channel, respectively. These results identify potential elements of plasma membrane quality control and indicate that cytoplasmic domains of membrane proteins are translocated into the vacuolar lumen.
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