Chen Esther J, Kaiser Chris A
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge 02139, USA.
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14837-42. doi: 10.1073/pnas.232591899. Epub 2002 Nov 4.
The delivery to the plasma membrane of the general amino acid permease, Gap1p, of Saccharomyces cerevisiae is regulated by the quality of the nitrogen source in the growth medium. In an effort to define how different nitrogen sources control Gap1p sorting, we find that mutations in GDH1 and GLN1 that decrease the flux through the glutamate and glutamine synthesis pathways result in increased Gap1p sorting to the plasma membrane. Conversely, deletion of MKS1, which increases glutamate and glutamine synthesis, decreases Gap1p sorting to the plasma membrane. Glutamate and glutamine are not unusual in their ability to regulate Gap1p sorting, because the addition of all natural amino acids and many amino acid analogs to the growth medium results in increased Gap1p sorting to the vacuole. Importantly, amino acids have the capacity to signal Gap1p sorting to the vacuole regardless of whether they can be used as a source of nitrogen. Finally, we show that rapamycin does not affect Gap1p sorting, indicating that Gap1p sorting is not directly influenced by the TOR pathway. Together, these data show that amino acids are a signal for sorting Gap1p to the vacuole and imply that the nitrogen-regulated Gap1p sorting machinery responds to amino acid-like compounds rather than to the overall nutritional status associated with growth on a particular nitrogen source.
酿酒酵母的通用氨基酸通透酶Gap1p向质膜的转运受生长培养基中氮源质量的调控。为了确定不同氮源如何控制Gap1p分选，我们发现GDH1和GLN1中的突变会降低谷氨酸和谷氨酰胺合成途径的通量，从而导致Gap1p向质膜的分选增加。相反，缺失MKS1会增加谷氨酸和谷氨酰胺的合成，减少Gap1p向质膜的分选。谷氨酸和谷氨酰胺在调节Gap1p分选方面的能力并非不同寻常，因为向生长培养基中添加所有天然氨基酸和许多氨基酸类似物会导致Gap1p向液泡的分选增加。重要的是，无论氨基酸是否可作为氮源，它们都有能力向液泡发出Gap1p分选的信号。最后，我们表明雷帕霉素不影响Gap1p分选，这表明Gap1p分选不受TOR途径的直接影响。总之，这些数据表明氨基酸是将Gap1p分选到液泡的信号，并暗示氮调节的Gap1p分选机制对氨基酸样化合物作出反应，而不是对与在特定氮源上生长相关的整体营养状况作出反应。
