Trs130 Participates in Autophagy Through GTPases Ypt31/32 in Saccharomyces cerevisiae
Trs130 Participates in Autophagy Through GTPases Ypt31/32 in Saccharomyces cerevisiae
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Trs130 通过 GTPases Ypt31/32 参与酿酒酵母的自噬
DOI：
10.1111/tra.12024
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发表时间：
2013-02-01
期刊：
影响因子：
4.5
通讯作者：
Xie, Zhiping
中科院分区：
文献类型：
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作者：
Zou, Shenshen;Chen, Yong;Xie, Zhiping
Trs130是转运蛋白颗粒II复合物的特异性组分，作为Rab GTPases Ypt31/32的鸟嘌呤核苷酸交换因子（GEF）。已知Ypt31/32参与自噬，但其确切机制尚未被彻底研究。在这项研究中，我们研究了Trs130在自噬中的潜在作用，发现在trs130ts （Trs130温度敏感）突变体中，细胞质-液泡靶向（Cvt）途径和饥饿诱导的自噬都存在缺陷。突变细胞不能将Atg8和Atg9正常运输到自噬体前结构/吞噬体组装位点（PAS），导致多个Atg8点和Atg9点分散在细胞质中。一些点被困在反高尔基体中。遗传学研究表明，Trs130突变对自噬途径的影响位于Atg5的下游，Atg1、Atg13、Atg9和Atg14的上游。此外，过表达Ypt31或Ypt32，而不表达Ypt1，可以挽救trs130ts和trs65ts （Trs130‐HA Trs120‐myc trs65Δ）突变体的自噬缺陷。我们的数据提供了Trs130参与自噬的机制，并表明由GTPases/GEFs调节的囊泡运输在自噬蛋白从反式高尔基体到PAS的运输中很重要。
Trs130 is a specific component of the transport protein particle II complex, which functions as a guanine nucleotide exchange factor (GEF) for Rab GTPases Ypt31/32. Ypt31/32 is known to be involved in autophagy, although the precise mechanism has not been thoroughly studied. In this study, we investigated the potential involvement of Trs130 in autophagy and found that both the cytoplasm‐to‐vacuole targeting (Cvt) pathway and starvation‐induced autophagy were defective in a trs130ts (trs130 temperature‐sensitive) mutant. Mutant cells could not transport Atg8 and Atg9 to the pre‐autophagosomal structure/phagophore assembly site (PAS) properly, resulting in multiple Atg8 dots and Atg9 dots dispersed in the cytoplasm. Some dots were trapped in the trans‐Golgi. Genetic studies showed that the effect of the Trs130 mutation was downstream of Atg5 and upstream of Atg1, Atg13, Atg9 and Atg14 on the autophagic pathway. Furthermore, overexpression of Ypt31 or Ypt32, but not of Ypt1, rescued autophagy defects in trs130ts and trs65ts (Trs130‐HA Trs120‐myc trs65Δ) mutants. Our data provide mechanistic insight into how Trs130 participates in autophagy and suggest that vesicular trafficking regulated by GTPases/GEFs is important in the transport of autophagy proteins from the trans‐Golgi to the PAS.