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Vrl1 relies on its VPS9‐domain to play a role in autophagy in Saccharomyces cerevisiae Saccharomyces cerevisiae

机译:VRL1依赖于其VPS9域在酿酒酵母酿酒酵母酿酒酵母酿酒酵母中发挥着自噬作用

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Abstract 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, V A R P‐ l ike 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 the VPS9 deletion. 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.
机译:摘要自噬是一种涉及许多ATG蛋白的细胞内降解过程,其分层招募以调节该过程。 Rab / YPT GTP酶及其活化剂,鸟嘌呤核苷酸交换因子(GEF)对于调节囊泡贩运至关重要,也涉及自噬。以前,我们报告了酵母VPS21及其全球环境基地VPS9进行自噬。后来,将含有第三酵母VPS9-结构域的蛋白质v A R P-L IKe 1(VRL1),其被鉴定为主要实验室菌株中的突变体,其部分与贩运过vps9的功能部分重叠。在本研究中,我们表明VRL1在自噬中进行了作用,其VPS9域对其在自噬中的作用至关重要。我们发现VRL1的定位不同于其他含有两个VPS9结构域的蛋白质,VPS9和MUK1,并且在饥饿后,仅VRL1从多点变为扩散。像VPS9一样,VRL1抑制了VPS9删除引起的自噬缺陷。我们进一步表明,这些VPS9-域域的蛋白质,VPS9,MUK1和VRL1,均在饥饿诱导的自噬的任何晚期中封闭细胞中的ATG8局部局部地定位,VRL1最常与ATG8共定位。通过自噬降解含VPS9结构域的蛋白质中的小部分(& 25%)。然而,大部分(& 60%)的VRL1独立于自噬减小。我们建议VRL1可以以与VPS9类似的方式调节自噬,并且VRL1的水平通过自动依赖性和依赖的路由部分减少。

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