Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast

In Saccharomyces cerevisiae, amino acid permeases are divided into two clas ses. One class, represented by the general amino acid permease GAP1, contai ns permeases regulated in response to the nitrogen source. The other class, including the high affinity tryptophan permease,TAT2, consists of the so-c alled constitutive permeases. We show that TAT2 is regulated at the level o f protein stability. In exponentially growing cells, TAT2 is in the plasma membrane and also accumulates in internal compartments of the secretory pat hway. Upon nutrient deprivation or rapamycin treatment,TAT2 is transported to and degraded in the vacuole. The ubiquitination machinery and lysine res idues within the NH2-terminal 31 amino acids of TAT2 mediate ubiquitination and degradation of the permease. Starvation-induced degradation of interna l TAT2 is blocked in sec18, sec23, pep12, and vps27 mutants, but not in sec 4, end4, and apg1 mutants, suggesting that, upon nutrient limitation, inter nal TAT2 is diverted from the late secretory pathway to the vacuolar pathwa y. Furthermore, our results suggest that TAT2 stability and sorting are con trolled by the TOR signaling pathway, and regulated inversely to that of GA P1.