The yeast arrestin-related protein Bul1 is a novel actor of glucose-induced endocytosis.
The yeast arrestin-related protein Bul1 is a novel actor of glucose-induced endocytosis.
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DOI：
10.1091/mbc.e17-07-0466
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发表时间：
2018-05-01
影响因子：
3.3
通讯作者：
Léon S
中科院分区：
文献类型：
--
作者：
Hovsepian J;Albanèse V;Becuwe M;Ivashov V;Teis D;Léon S
Bul1是葡萄糖诱导内吞作用的新参与者，主要在Jen1内化过程中作用于质膜。Bul1作为另一种葡萄糖调节的ART蛋白Rod1的替代适配器，使葡萄糖诱导的内吞作用过程具有稳健性。酵母细胞具有显著的适应环境营养变化的能力。在适应过程中，营养信号通路驱动存在于细胞表面的营养转运体的选择性内吞。当前的一个挑战是理解这一规则的机制基础。转运蛋白内吞作用是由它们的泛素化引发的，这涉及到泛素连接酶Rsp5和它的阻滞相关家族（ART）的接头。这一步骤受到养分供应的高度调节。例如，单羧酸转运体Jen1在暴露于葡萄糖时被泛素化、内吞和降解。整个过程需要ART蛋白Rod1；然而，Rod1在后来的内吞途径中控制着Jen1的转运，并且对于Jen1的内化几乎是必不可少的。因此，葡萄糖如何触发Jen1内化仍不清楚。我们报告了另一个名为Bul1的ART，但不是它的平行体Bul2，有助于Jen1的内在化。Bul1响应葡萄糖可用性，并优先在质膜上作用于Jen1内化。因此，多种art可沿内吞途径依次作用以控制转运体稳态。此外，在环己亚胺处理后，Bul1负责Jen1的内吞作用，这表明art的功能冗余可能是由于它们在不同条件下与多种载物相互作用的能力。
Bul1 is identified as a novel actor in glucose-induced endocytosis, mainly acting at the plasma membrane in the process of Jen1 internalization. Bul1 acts as an alternate adaptor for another glucose-regulated ART protein, Rod1, to allow robustness in the process of glucose-induced endocytosis. Yeast cells have a remarkable ability to adapt to nutritional changes in their environment. During adaptation, nutrient-signaling pathways drive the selective endocytosis of nutrient transporters present at the cell surface. A current challenge is to understand the mechanistic basis of this regulation. Transporter endocytosis is triggered by their ubiquitylation, which involves the ubiquitin ligase Rsp5 and its adaptors of the arrestin-related family (ART). This step is highly regulated by nutrient availability. For instance, the monocarboxylate transporter Jen1 is ubiquitylated, endocytosed, and degraded upon exposure to glucose. The ART protein Rod1 is required for this overall process; yet Rod1 rather controls Jen1 trafficking later in the endocytic pathway and is almost dispensable for Jen1 internalization. Thus, how glucose triggers Jen1 internalization remains unclear. We report that another ART named Bul1, but not its paralogue Bul2, contributes to Jen1 internalization. Bul1 responds to glucose availability, and preferentially acts at the plasma membrane for Jen1 internalization. Thus, multiple ARTs can act sequentially along the endocytic pathway to control transporter homeostasis. Moreover, Bul1 is in charge of Jen1 endocytosis after cycloheximide treatment, suggesting that the functional redundancy of ARTs may be explained by their ability to interact with multiple cargoes in various conditions.