Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter.
Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter.
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DOI：
10.1242/bio.20148367
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发表时间：
2014-05-29
期刊：
影响因子：
2.4
通讯作者：
Kikkawa U
中科院分区：
文献类型：
--
作者：
Nakashima A;Kamada S;Tamanoi F;Kikkawa U
与人类结节性硬化症复合体蛋白同源的TSC1-TSC2复合体通过调节裂殖酵母中氨基酸转运体的表达和细胞内分布来调控氨基酸的摄取。在这里，我们对参与氨基酸摄取的分子进行了遗传筛选，发现了Arn1(也称为Any1)。Arn1与酿酒酵母Art1同源，Art1是酿酒酵母中与arrestin相关的运输适配器(ART)，它含有一个保守的arrestin基序、一个泛素化位点和两个PY基序。Arn1+的过度表达增强了细胞对刀豆碱的抗性，而它的破坏则导致了对刀豆碱的超敏。我们还发现Arn1调节Cat1氨基酸转运体的内吞作用。此外，Arn1+的缺失抑制了Tsc2Δ中氨基酸摄取的缺陷和Cat1的异常定位。Arn1与Pub1泛素连接酶相互作用并被其泛素化，而Pub1泛素连接酶是调节Cat1内吞所必需的。Cat1在N-末端的赖氨酸残基上进行泛素化，这部分是由Arn1介导的，以确定Cat1的定位。正确地说，Arn1是一种在S.pombe中的ART，通过调节TSC2参与的Cat1内吞作用促进氨基酸的摄取。
The Tsc1–Tsc2 complex homologous to human tuberous sclerosis complex proteins governs amino acid uptake by regulating the expression and intracellular distribution of amino acid transporters in Schizosaccharomyces pombe. Here, we performed a genetic screening for molecules that are involved in amino acid uptake and found Arn1 (also known as Any1). Arn1 is homologous to ART1, an arrestin-related trafficking adaptor (ART) in Saccharomyces cerevisiae, and contains a conserved arrestin motif, a ubiquitination site, and two PY motifs. Overexpression of arn1+ confers canavanine resistance on cells, whereas its disruption causes hypersensitivity to canavanine. We also show that Arn1 regulates endocytosis of the Cat1 amino acid transporter. Furthermore, deletion of arn1+ suppresses a defect of amino acid uptake and the aberrant Cat1 localization in tsc2Δ. Arn1 interacts with and is ubiquitinated by the Pub1 ubiquitin ligase, which is necessary to regulate Cat1 endocytosis. Cat1 undergoes ubiquitinations on lysine residues within the N-terminus, which are mediated, in part, by Arn1 to determine Cat1 localization. Correctively, Arn1 is an ART in S. pombe and contributes to amino acid uptake through regulating Cat1 endocytosis in which Tsc2 is involved.
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影响因子：
4
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Yanagida, Mitsuhiro