title: Different effects of Atg2 and Atg18 mutations on Atg8a and Atg9 trafficking during starvation in Drosophila.
abstract: The Atg2-Atg18 complex acts in parallel to Atg8 and regulates Atg9 recycling from phagophore assembly site (PAS) during autophagy in yeast. Here we show that in Drosophila, both Atg9 and Atg18 are required for Atg8a puncta formation, unlike Atg2. Selective autophagic degradation of ubiquitinated proteins is mediated by Ref(2)P/p62. The transmembrane protein Atg9 accumulates on refractory to Sigma P (Ref(2)P) aggregates in Atg7, Atg8a and Atg2 mutants. No accumulation of Atg9 is seen on Ref(2)P in cells lacking Atg18 or Vps34 lipid kinase function, while the Atg1 complex subunit FIP200 is recruited. The simultaneous interaction of Atg18 with both Atg9 and Ref(2)P raises the possibility that Atg18 may facilitate selective degradation of ubiquitinated protein aggregates by autophagy.
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Hegedűs
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pircs
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Varga
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary. Electronic address: szmrt@elte.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport; D059748:Proteolysis; D013217:Starvation / Q000235:genetics; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C587330:Atg18a protein, Drosophila; C550900:Atg2 protein, Drosophila; C527373:Atg8a protein, Drosophila; C557894:Atg9 protein, Drosophila; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D057149:Ubiquitinated Proteins
keywords: Atg; Atg18; Atg2; Atg7; Atg8a; Atg9; PAS; PI3P; Ref(2)P; Ref(2)P/p62; ULK; Vps; WD40 repeat domain phosphoinositide-interacting protein; WIPI; autophagy-related; phagophore assembly site; phosphatidylinositol 3-phosphate; refractory to Sigma P; uncoordinated-51 like autophagy kinase; vacuolar protein sorting