title: Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy.
abstract: 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.
authors.affiliation: Life Sciences Institute and Departments of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Per E
authors.initials: PE
authors.lastname: Strømhaug
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.forename: Ju
authors.initials: J
authors.lastname: Guan
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Wang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism*; D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D002462:Cell Membrane / Q000502:physiology; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D050356:Lipid Metabolism; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D010588:Phagosomes / Q000737:chemistry / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014617:Vacuoles / Q000737:chemistry / Q000502:physiology
chemical_list: C441008:ATG18 protein, S cerevisiae; C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010716:Phosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; C450423:ATG21 protein, S cerevisiae; D010450:Endopeptidases; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae