Methionine triggers Ppz-mediated dephosphorylation of Art1 to promote cargo-specific endocytosis
Methionine triggers Ppz-mediated dephosphorylation of Art1 to promote cargo-specific endocytosis
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DOI：
10.1083/jcb.201712144
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发表时间：
2019-03-01
影响因子：
7.8
通讯作者：
MacGurn, Jason A.
中科院分区：
文献类型：
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作者：
Lee, Sora;Ho, Hsuan-Chung;MacGurn, Jason A.
通过选择性内吞作用调节质膜(PM)蛋白的丰度，对于细胞适应胁迫或改变营养物质的可获得性至关重要。一个例子涉及酵母蛋氨酸转运体Mup1的快速内吞周转，以响应蛋氨酸供应的增加。在这里，我们报告蛋氨酸触发泛素连接酶适配器Art1快速易位到PM，并在特定的苏氨酸残基上使Art1去磷酸化。这种蛋氨酸诱导的Art1去磷酸化是由Ppz磷酸酶介导的，并且对Art1的模拟磷酸化和磷酸化缺陷变体的分析表明，这些事件在PM触发了Art1对Mup1的识别重要的是，我们发现Ppz磷酸酶对于Art1 PM易位是必不可少的，但对于Art1与Mup1的相互作用是必需的。根据我们的发现，我们认为蛋氨酸的流入触发了Art1到PM的易位，随后Ppz介导的去磷酸化促进了PM的货物识别
Regulation of plasma membrane (PM) protein abundance by selective endocytosis is critical for cellular adaptation to stress or changing nutrient availability. One example involves rapid endocytic turnover of Mup1, a yeast methionine transporter, in response to increased methionine availability. Here, we report that methionine triggers rapid translocation of the ubiquitin ligase adaptor Art1 to the PM and dephosphorylation of Art1 at specific threonine residues. This methionine-induced dephosphorylation of Art1 is mediated by Ppz phosphatases, and analysis of phosphomimetic and phosphorylation-defective variants of Art1 indicates that these events toggle Art1 recognition of Mup1 at the PM. Importantly, we find that Ppz phosphatases are dispensable for Art1 PM translocation, but are required for Art1 interaction with Mup1. Based on our findings, we propose that methionine influx triggers Art1 translocation to the PM, followed by Ppz-mediated dephosphorylation which promotes cargo recognition at the PM.