Phosphorylation of phosphatidylinositol (PtdIns) by a PtdIns 3-kinase is an essential process in autophagy. Atg14, a specific subunit of one of the PtdIns 3-kinase complexes, targets the complex to the probable site of autophagosome formation, thereby, sorting the complex to function specifically in autophagy. The N-terminal half of Atg14, containing coiled-coil domains, is required to form the PtdIns 3-kinase complex and target it to the proper site. The C-terminal half of yeast Atg14 is suggested to be involved in the formation of a normal-sized autophagosome. The C-terminal half of mammalian Atg14 contains the Barkor/Atg14(L) autophagosome-targeting sequence (BATS) domain that preferentially binds to the highly curved membranes containing PtdIns(3)P and is proposed to target the PtdIns 3-kinase complex efficiently to the isolation membrane. Thus, the N- and C-terminal halves of Atg14 are likely to have an essential core function and a regulatory role, respectively. 1. PtdIns 3-Kinase in Autophagy Eukaryotic cells can enclose their own cytoplasmic components in a double-membrane structure, the autophagosome, and deliver it to a lytic compartment, the vacuole/lysosome, where the contents are then degraded. This conserved system is involved not only in the recycling of proteins under starvation conditions but also in the clearance of organelles and aberrant aggregate-prone proteins, digestion of invading pathogens, and so on [1–4]. Genes involved in autophagy were first identified by yeast genetic screenings [5–7]. At present, more than 30 autophagy-related (ATG) genes have been identified in yeast, and of them at least 18 genes are essential for autophagosome formation, a crucial process in autophagy. Most of these 18 genes are conserved in mammals, suggesting that the mechanism of autophagosome formation is basically conserved from yeast to mammals. The 18 Atg proteins can be divided into five groups according to their functions [8, 9]. One group consists of subunits of a class III phosphatidylinositol (PtdIns) 3-kinase complex (hereafter, PtdIns 3-kinase indicates the class III PtdIns 3-kinase). Atg14 and Vps30/Atg6 are two such proteins and are included in this group together with Vps34 and Vps15, catalytic and regulatory subunits, respectively, (the functions of Vps34 and Vps15 in the vacuolar protein sorting pathway have been studied in detail, and; thus, they are not designated as Atg proteins although they are essential for autophagy). Atg14 is a key subunit in determining the function of the PtdIns 3-kinase complex and is the focus of this
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