TRAPPIII is responsible for vesicular transport from early endosomes to Golgi, facilitating Atg9 cycling in autophagy
TRAPPIII is responsible for vesicular transport from early endosomes to Golgi, facilitating Atg9 cycling in autophagy
复制标题
DOI：
10.1242/jcs.131318
复制
发表时间：
2013-11
影响因子：
4
通讯作者：
Kanae Shirahama‐Noda;S. Kira;T. Yoshimori;T. Noda
中科院分区：
文献类型：
--
作者：
Kanae Shirahama‐Noda;S. Kira;T. Yoshimori;T. Noda
摘要自噬是一个受多种因素调控的蛋白质大量降解过程。在这项研究中，我们定量评估了每个必需酵母基因对自噬的贡献。在我们确定的影响因素中，我们重点研究了TRAPPIII复合体，最近发现它是RAB小GTP酶Ypt1的鸟嘌呤核苷酸交换因子。在营养丰富的条件下(CVT途径)，TRAPPIII突变体的自噬是有缺陷的，但饥饿诱导的自噬只受到部分影响。在这里，我们展示了TRAPPIII在高尔基复合体中的功能，从早期的内体接收一般的逆行囊泡运输。在这个依赖于TRAPPIII的途径中，货物蛋白包括Atg9，一种对自噬至关重要的跨膜蛋白，以及Snc1，一种与自噬无关的陷阱。当细胞饥饿时，囊泡从晚期内体到高尔基体的运动进一步中断，导致Atg9运输和自噬的缺陷。因此，在营养丰富的条件下，依赖于TRAPPIII的分选途径为Atg9提供了自噬前结构和噬菌体组装部位，而在营养有限的情况下，内体到高尔基体的晚期途径被添加到这些储存库中。这种对TRAPPIII作用的澄清阐明了一般的膜交通是如何促进自噬的。
Summary Autophagy is a bulk protein-degradation process that is regulated by many factors. In this study, we quantitatively assessed the contribution of each essential yeast gene to autophagy. Of the contributing factors that we identified, we focused on the TRAPPIII complex, which was recently shown to act as a guanine-nucleotide exchange factor for the Rab small GTPase Ypt1. Autophagy is defective in the TRAPPIII mutant under nutrient-rich conditions (Cvt pathway), but starvation-induced autophagy is only partially affected. Here, we show that TRAPPIII functions at the Golgi complex to receive general retrograde vesicle traffic from early endosomes. Cargo proteins in this TRAPPIII-dependent pathway include Atg9, a transmembrane protein that is essential for autophagy, and Snc1, a SNARE unrelated to autophagy. When cells were starved, further disruption of vesicle movement from late endosomes to the Golgi caused defects in Atg9 trafficking and autophagy. Thus, TRAPPIII-dependent sorting pathways provide Atg9 reservoirs for pre-autophagosomal structure and phagophore assembly sites under nutrient-rich conditions, whereas the late endosome-to-Golgi pathway is added to these reservoirs when nutrients are limited. This clarification of the role of TRAPPIII elucidates how general membrane traffic contributes to autophagy.