title: The putative HORMA domain protein Atg101 dimerizes and is required for starvation-induced and selective autophagy in Drosophila.
abstract: The large-scale turnover of intracellular material including organelles is achieved by autophagy-mediated degradation in lysosomes. Initiation of autophagy is controlled by a protein kinase complex consisting of an Atg1-family kinase, Atg13, FIP200/Atg17, and the metazoan-specific subunit Atg101. Here we show that loss of Atg101 impairs both starvation-induced and basal autophagy in Drosophila. This leads to accumulation of protein aggregates containing the selective autophagy cargo ref(2)P/p62. Mapping experiments suggest that Atg101 binds to the N-terminal HORMA domain of Atg13 and may also interact with two unstructured regions of Atg1. Another HORMA domain-containing protein, Mad2, forms a conformational homodimer. We show that Drosophila Atg101 also dimerizes, and it is predicted to fold into a HORMA domain. Atg101 interacts with ref(2)P as well, similar to Atg13, Atg8a, Atg16, Atg18, Keap1, and RagC, a known regulator of Tor kinase which coordinates cell growth and autophagy. These results raise the possibility that the interactions and dimerization of the putative HORMA domain protein Atg101 play critical roles in starvation-induced autophagy and proteostasis, by promoting the formation of protein aggregate-containing autophagosomes.
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest 1117, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Hegedűs
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest 1117, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest 1083, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gáspári
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest 1117, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D019281:Dimerization; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D014617:Vacuoles / Q000378:metabolism
chemical_list: C000594170:Atg101 protein, Drosophila; C541704:Atg13 protein, Drosophila; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins