Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids
Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids
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DOI：
10.7554/elife.58246
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发表时间：
2020-08-03
期刊：
影响因子：
7.7
通讯作者：
Teis, David
中科院分区：
文献类型：
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作者：
Ivashov, Vasyl;Zimmer, Johannes;Teis, David
细胞如何调节其膜上的营养物质运输尚不完全清楚。此前，我们已经证明，酿酒酵母通过内吞糖和氨基酸转运蛋白(AATS)，广泛地重新配置质膜上的营养转运蛋白，以响应氨基酸的可获得性(Muller等人，2015)。全基因组筛选显示，四种AAT在饥饿期间的选择性内吞作用需要α-arrestin家族蛋白Art2/Ecm21，它是泛素连接酶Rsp5的接头，并通过一般的氨基酸控制途径进行诱导。Art2使用碱性补丁来识别AATS中的C-末端酸性排序基序，从而指示Rsp5泛素化近端赖氨酸残基。当氨基酸过多时，RSP5相反地使用TORC1激活的Art1来检测同一AAT中的N-末端酸性排序基序，这会启动排他性底物诱导的内吞作用。因此，氨基酸过量或饥饿激活了互补的α-arrestin-Rsp5-复合体，以控制选择性的内吞作用和适应营养的获取。
How cells adjust nutrient transport across their membranes is incompletely understood. Previously, we have shown that S. cerevisiae broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through endocytosis of sugar- and amino acid transporters (AATs) (Muller et al., 2015). A genome-wide screen now revealed that the selective endocytosis of four AATs during starvation required the alpha-arrestin family protein Art2/Ecm21, an adaptor for the ubiquitin ligase Rsp5, and its induction through the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in AATs and thereby instructs Rsp5 to ubiquitinate proximal lysine residues. When amino acids are in excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis. Thus, amino acid excess or starvation activate complementary alpha-arrestin-Rsp5-complexes to control selective endocytosis and adapt nutrient acquisition.