ENDOCYTOSIS AND DEGRADATION OF THE YEAST URACIL PERMEASE UNDER ADVERSE CONDITIONS

Yeast uracil permease follows the secretory pathway to the plasma memb rane and is phosphorylated on serine residues in a post-Golgi compartm ent. The protein was found to be rather stable in growing cells, but i ts turnover rate (half-life of about 7 h) was much faster than that of most yeast proteins. Several adverse conditions triggered the rapid d egradation of uracil permease, and so a loss of uracil uptake. Turnove r was rapid when yeast cells were starved of either nitrogen, phosphat e, or carbon, and as they approached the stationary growth phase. Rapi d permease degradation was also promoted by the inhibition of protein synthesis. The degradation of uracil permease in response to several s tresses was strikingly slower in the two mutants, end3 and end4, that are deficient in the internalization step of receptor-mediated endocyt osis. Thus, internalization is the first step in the permease degradat ive pathway. Uracil permease is degraded in the vacuole, since pep4 mu tant cells lacking vacuolar protease activities accumulated large amou nts of uracil permease, which was located within the vacuole by immuno fluorescence. We have yet to determine whether adverse conditions enha nce permease endocytosis and subsequent degradation or divert internal ized uracil permease from a recycling to a degradative pathway.