Departments of Molecular, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7811-6. doi: 10.1073/pnas.1000063107. Epub 2010 Apr 7.
Macroautophagy (hereafter autophagy) is a ubiquitous process in eukaryotic cells that is integrally involved in various aspects of cellular and organismal physiology. The morphological hallmark of autophagy is the formation of double-membrane cytosolic vesicles, autophagosomes, which sequester cytoplasmic cargo and deliver it to the lysosome or vacuole. Thus, autophagy involves dynamic membrane mobilization, yet the source of the lipid that forms the autophagosomes and the mechanism of membrane delivery are poorly characterized. The TRAPP complexes are multimeric guanine nucleotide exchange factors (GEFs) that activate the Rab GTPase Ypt1, which is required for secretion. Here we describe another form of this complex (TRAPPIII) that acts as an autophagy-specific GEF for Ypt1. The Trs85 subunit of the TRAPPIII complex directs this Ypt1 GEF to the phagophore assembly site (PAS) that is involved in autophagosome formation. Consistent with the observation that a Ypt1 GEF is directed to the PAS, we find that Ypt1 is essential for autophagy. This is an example of a Rab GEF that is specifically targeted for canonical autophagosome formation.
自噬（下文简称自噬）是真核细胞中普遍存在的一种过程，它与细胞和生物体生理学的各个方面都有密切关系。自噬的形态学标志是双层细胞质囊泡的形成，即自噬体，它可以隔离细胞质中的货物并将其递送至溶酶体或液泡中。因此，自噬涉及动态膜的动员，但形成自噬体的脂质来源以及膜递送的机制仍不清楚。TRAPP 复合物是多聚鸟嘌呤核苷酸交换因子（GEFs），可以激活 Rab GTPase Ypt1，而 Ypt1 是分泌所必需的。在这里，我们描述了这种复合物的另一种形式（TRAPPIII），它作为 Ypt1 的一种自噬体特异性 GEF。TRAPPIII 复合物的 Trs85 亚基将这种 Ypt1 GEF 引导到参与自噬体形成的噬菌斑组装位点（PAS）。与观察到 Ypt1 GEF 被引导到 PAS 的结果一致，我们发现 Ypt1 对于自噬是必需的。这是一个 Rab GEF 被专门靶向用于经典自噬体形成的例子。
