Endosomal recycling maintains the cell surface abundance of nutrient transporters for nutrient uptake, but how the cell integrates nutrient availability with recycling is less well understood. Here, in studying the recycling of human glutamine transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), SNAT1 (SLC38A1), and SNAT2 (SLC38A2), we establish that following amino acid restriction, the adaptive delivery of SNAT2 to the cell surface relies on retromer, a master conductor of endosomal recycling. Upon complete amino acid starvation or selective glutamine depletion, we establish that retromer expression is upregulated by transcription factor EB (TFEB) and other members of the MiTF/TFE family of transcription factors through association with CLEAR elements in the promoters of the retromer genes VPS35 and VPS26A. TFEB regulation of retromer expression therefore supports adaptive nutrient acquisition through endosomal recycling.

中文翻译：

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TFEB 控制逆转录酶表达以响应营养可用性

内体回收维持细胞表面营养转运蛋白的丰度以促进营养吸收，但细胞如何将营养可用性与回收相结合尚不清楚。在此，在研究人谷氨酰胺转运蛋白 ASCT2 (SLC1A5)、LAT1 (SLC7A5)、SNAT1 (SLC38A1) 和 SNAT2 (SLC38A2) 的循环利用时，我们确定，在氨基酸限制后，SNAT2 向细胞表面的适应性递送依赖于逆转录酶，内体回收的主要指挥者。在完全氨基酸饥饿或选择性谷氨酰胺耗尽后，我们确定转录因子 EB (TFEB) 和 MiTF/TFE 转录因子家族的其他成员通过与逆转录酶基因 VPS35 和VPS26A。因此，TFEB 对逆转录体表达的调节支持通过内体循环获得适应性营养。