Vrl1 relies on its VPS9-domain to play a role in autophagy in Saccharomyces cerevisiae
Vrl1 relies on its VPS9-domain to play a role in autophagy in Saccharomyces cerevisiae
复制标题
Vrl1 依靠其 VPS9 结构域在酿酒酵母自噬中发挥作用
DOI：
10.1002/cbin.11156
复制
发表时间：
2019
影响因子：
3.9
通讯作者：
Liang Yongheng
中科院分区：
文献类型：
--
作者：
Li Wenjing;Wu Zulin;Liang Yongheng
自噬是一个细胞内降解过程，涉及许多Atg蛋白，这些蛋白被分级招募来调节这一过程。Rab/Ypt GTP酶及其激活剂鸟嘌呤核苷酸交换因子（GEF）对调节囊泡运输至关重要，也参与自噬。之前，我们报道了酵母Vps 21及其GEF Vps 9是自噬所必需的。后来，第三种酵母VPS 9结构域蛋白质VARP样1（Vrl 1）被鉴定为主要实验室菌株的突变体，在运输中与Vps 9具有部分重叠的功能。在这项研究中，我们发现Vrl 1在自噬中发挥作用，其VPS 9结构域对其在自噬中的作用至关重要。我们发现，Vrl 1的定位不同于其他两种含有VPS 9结构域的蛋白，Vps 9和Muk 1，只有Vrl 1在饥饿后从多点变为扩散。与Vps 9一样，Vrl 1抑制Vps 9缺失引起的自噬缺陷。我们进一步表明，这些含有VPS 9结构域的蛋白质，Vps 9，Muk 1和Vrl 1，都与Atg 8共定位在饥饿诱导的自噬的任何后期步骤中被阻断的细胞中的自噬体上，其中Vrl 1最常与Atg 8共定位。这些含有VPS 9结构域的蛋白质中的一小部分（<25%）通过自噬降解。然而，很大一部分（>60%）的Vrl 1独立于自噬而下降。我们认为，Vrl 1可能以与Vps 9类似的方式调节自噬，并且Vrl 1的水平部分通过自噬依赖性和非依赖性途径降低。
Autophagy is an intracellular degradation process involving many Atg proteins, which are recruited hierarchically to regulate this process. Rab/Ypt GTPases and their activators, guanine nucleotide exchange factors (GEFs), which are critical for regulating vesicle trafficking, are also involved in autophagy. Previously, we reported that yeast Vps21 and its GEF Vps9 are required for autophagy. Later, a third yeast VPS9‐domain‐containing protein,VARP‐like 1 (Vrl1), which was identified as a mutant in major laboratory strains, had partially overlapping functions with Vps9 in trafficking. In this study, we showed that Vrl1 performed roles in autophagy, and its VPS9‐domain was crucial for its role in autophagy. We found that localization of Vrl1 differed from the other two VPS9‐domain‐containing proteins, Vps9 and Muk1, and only Vrl1 changed from multipoint to diffusion after starvation. Like Vps9, Vrl1 suppressed autophagic defects caused by theVPS9deletion. We further showed that these VPS9‐domain‐containing proteins, Vps9, Muk1, and Vrl1, all co‐localized with Atg8 on autophagosomes in cells blocked in any late step of starvation‐induced autophagy, with Vrl1 most often co‐localizing with Atg8. A small portion (<25%) of these VPS9‐domain‐containing proteins were degraded through autophagy. However, a large portion (>60%) of Vrl1 decreased independently of autophagy. We propose that Vrl1 may regulate autophagy in a similar way as Vps9, and the level of Vrl1 partly decreases through both autophagy‐dependent and ‐independent routes.