Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast
Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast
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DOI：
10.1083/jcb.146.6.1227
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发表时间：
1999-09-20
影响因子：
7.8
通讯作者：
Hall, MN
中科院分区：
文献类型：
--
作者：
Beck, T;Schmidt, A;Hall, MN
在酿酒酵母中，氨基酸渗透酶分为两类。一类，由一般的氨基酸通透酶GAP 1代表，含有响应于氮源调节的通透酶。另一类，包括高亲和力色氨酸通透酶，TAT 2，由所谓的组成型通透酶组成。我们表明，TAT 2在蛋白质稳定性水平上受到调节。在指数生长的细胞中，TAT 2位于质膜中，并且也在分泌途径的内部隔室中积累。在营养剥夺或雷帕霉素处理后，TAT 2被运输到液泡并在液泡中降解。泛素化机制和TAT 2的NH 2-末端31个氨基酸内的赖氨酸残基介导通透酶的泛素化和降解。饥饿诱导降解的内部TAT 2被阻断在sec 18，sec 23，pep 12，和vps 27突变体，但不是在sec 4，end 4，和apg 1突变体，这表明，在营养限制，内部TAT 2是从后期分泌途径转移到液泡途径。此外，我们的研究结果表明，TAT 2的稳定性和分选是由TOR信号通路控制的，并且与GAP 1的调节相反。
In Saccharomyces cerevisiae, amino acid permeases are divided into two classes. One class, represented by the general amino acid permease GAP1, contains permeases regulated in response to the nitrogen source. The other class, including the high affinity tryptophan permease,TAT2, consists of the so-called constitutive permeases. We show that TAT2 is regulated at the level of protein stability. In exponentially growing cells, TAT2 is in the plasma membrane and also accumulates in internal compartments of the secretory pathway. Upon nutrient deprivation or rapamycin treatment,TAT2 is transported to and degraded in the vacuole. The ubiquitination machinery and lysine residues within the NH2-terminal 31 amino acids of TAT2 mediate ubiquitination and degradation of the permease. Starvation-induced degradation of internal TAT2 is blocked in sec18, sec23, pep12, and vps27 mutants, but not in sec4, end4, and apg1 mutants, suggesting that, upon nutrient limitation, internal TAT2 is diverted from the late secretory pathway to the vacuolar pathway. Furthermore, our results suggest that TAT2 stability and sorting are controlled by the TOR signaling pathway, and regulated inversely to that of GAP1.