Strømhaug Per E, Reggiori Fulvio, Guan Ju, Wang Chao-Wen, Klionsky Daniel J
Life Sciences Institute and Departments of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Mol Biol Cell. 2004 Aug;15(8):3553-66. doi: 10.1091/mbc.e04-02-0147. Epub 2004 May 21.
Delivery of proteins and organelles to the vacuole by autophagy and the cytoplasm to vacuole targeting (Cvt) pathway involves novel rearrangements of membrane resulting in the formation of vesicles that fuse with the vacuole. The mechanism of vesicle formation and the origin of the membrane are complex issues still to be resolved. Atg18 and Atg21 are proteins essential to vesicle formation and together with Ygr223c form a novel family of phosphoinositide binding proteins that are associated with the vacuole and perivacuolar structures. Their localization requires the activity of Vps34, suggesting that phosphatidylinositol(3)phosphate may be essential for their function. The activity of Atg18 is vital for all forms of autophagy, whereas Atg21 is required for the Cvt pathway but not for nitrogen starvation-induced autophagy. The loss of Atg21 results in the absence of Atg8 from the pre-autophagosomal structure (PAS), which may be ascribed to a reduced rate of conjugation of Atg8 to phosphatidylethanolamine. A similar defect in localization of a second ubiquitin-like conjugate, Atg12-Atg5, suggests that Atg21 may be involved in the recruitment of membrane to the PAS.
通过自噬以及细胞质到液泡靶向（Cvt）途径将蛋白质和细胞器递送至液泡，涉及膜的新重排，从而导致形成与液泡融合的囊泡。囊泡形成的机制以及膜的来源是仍有待解决的复杂问题。Atg18和Atg21是囊泡形成所必需的蛋白质，它们与Ygr223c一起形成了一个新的磷酸肌醇结合蛋白家族，这些蛋白与液泡和液泡周围结构相关。它们的定位需要Vps34的活性，这表明磷脂酰肌醇-3-磷酸可能对其功能至关重要。Atg18的活性对所有形式的自噬都至关重要，而Atg21是Cvt途径所必需的，但对氮饥饿诱导的自噬则不是必需的。Atg21的缺失导致自噬前体结构（PAS）中没有Atg8，这可能归因于Atg8与磷脂酰乙醇胺结合率的降低。第二种泛素样缀合物Atg12-Atg5定位的类似缺陷表明，Atg21可能参与将膜募集到PAS。
