TORC2 inhibition of α-arrestin Aly3 mediates cell surface persistence of S. pombe Ght5 glucose transporter in low glucose
TORC2 inhibition of α-arrestin Aly3 mediates cell surface persistence of S. pombe Ght5 glucose transporter in low glucose
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DOI：
10.1242/jcs.257485
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发表时间：
2021-05-01
影响因子：
4
通讯作者：
Saitoh, Shigeaki
中科院分区：
文献类型：
--
作者：
Toyoda, Yusuke;Soejima, Saeko;Saitoh, Shigeaki
在裂殖酵母，裂殖酵母，高亲和力己糖转运蛋白，Ght 5，必须转录上调和定位到细胞表面的细胞分裂在有限的葡萄糖。虽然Ght 5的细胞表面定位依赖于雷帕霉素复合物2的靶点（TORC 2），但TORC 2确保Ght 5正确定位的分子机制仍然未知。我们进行了基因突变，恢复Ght 5定位在TORC 2缺陷突变细胞的细胞表面上的基因筛选，并确定了一个基因编码一个未知的α-抑制蛋白样蛋白，Aly 3/SPCC 584.15 c。α-抑制蛋白被认为募集泛素连接酶到膜相关蛋白。同样，Ght 5在TORC 2缺陷细胞中被泛素化，并且这种泛素化依赖于Aly 3。据推测，TORC 2通过阻止Aly 3依赖的泛素化和随后的Ght 5向液泡的泛素化依赖的易位，使Ght 5能够在细胞表面定位。令人惊讶的是，氮饥饿，而不是葡萄糖消耗，触发铝3依赖的Ght 5运输到液泡中的S。粟酒裂殖酵母，不像芽殖酵母己糖转运蛋白，其液泡转运是在己糖浓度变化时启动的。这项研究提供了新的见解的分子机制控制的亚细胞定位的己糖转运蛋白响应细胞外刺激。
In the fission yeast, Schizosaccharomyces pombe, the high-affinity hexose transporter, Ght5, must be transcriptionally upregulated and localized to the cell surface for cell division under limited glucose. Although cell-surface localization of Ght5 depends on Target of rapamycin complex 2 (TORC2), the molecular mechanisms by which TORC2 ensures proper localization of Ght5 remain unknown. We performed genetic screening for gene mutations that restore Ght5 localization on the cell surface in TORC2-deficient mutant cells, and identified a gene encoding an uncharacterized alpha-arrestin-like protein, Aly3/SPCC584.15c. alpha-arrestins are thought to recruit a ubiquitin ligase to membrane-associated proteins. Consistently, Ght5 is ubiquitylated in TORC2-deficient cells, and this ubiquitylation is dependent on Aly3. TORC2 supposedly enables cell-surface localization of Ght5 by preventing Aly3-dependent ubiquitylation and subsequent ubiquitylation-dependent translocation of Ght5 to vacuoles. Surprisingly, nitrogen starvation, but not glucose depletion, triggers Aly3-dependent transport of Ght5 to vacuoles in S. pombe, unlike budding yeast hexose transporters, vacuolar transport of which is initiated upon changes in hexose concentration. This study provides new insights into the molecular mechanisms controlling the subcellular localization of hexose transporters in response to extracellular stimuli.