title: PP2A regulates autophagy in two alternative ways in Drosophila.
abstract: Protein phosphatase 2A (PP2A) holoenzyme is a heterotrimeric complex, consisting of A, B and C subunits. The catalytic subunit PP2A-C (microtubule star/mts) binds to the C-terminal part of the scaffold protein PP2A-A (PP2A-29B). In Drosophila, there are three different forms of B subunits (widerborst/wdb, twins/tws and PP2A-B'), which determine the subcellular localization and substrate specificity of the holoenzyme. Previous studies demonstrated that PP2A is involved in the control of TOR-dependent autophagy both in yeast and mammals. Furthermore, in Drosophila, wdb genetically interacts with the PtdIns3K/PTEN/Akt signaling cascade, which is a main upstream regulatory system of dTOR. Here we demonstrate that in Drosophila, two different PP2A complexes (containing B' or wdb subunit) play essential roles in the regulation of starvation-induced autophagy. The PP2A-A/wdb/C complex acts upstream of dTOR, whereas the PP2A-A/B'/C complex functions as a target of dTOR and may regulate the elongation of autophagosomes and their subsequent fusion with lysosomes. We also identified three Drosophila Atg orthologs (Atg14, Atg17 and Atg101), which represent potential targets of the PP2A-A/B'/C complex during autophagy.
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Bánréti
authors.forename: Tamás
authors.initials: T
authors.lastname: Lukácsovich
authors.forename: György
authors.initials: G
authors.lastname: Csikós
authors.forename: Miklós
authors.initials: M
authors.lastname: Erdélyi
authors.forename: Miklós
authors.initials: M
authors.lastname: Sass
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D050980:GATA Transcription Factors / Q000378:metabolism; D005799:Genes, Dominant; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008561:Membrane Fusion / Q000187:drug effects; D008954:Models, Biological; D019319:Okadaic Acid / Q000494:pharmacology; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
chemical_list: C000594170:Atg101 protein, Drosophila; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D050980:GATA Transcription Factors; D021122:Protein Subunits; C529534:mts protein, Drosophila; C103965:srp protein, Drosophila; D019319:Okadaic Acid; D054648:Protein Phosphatase 2; D020123:Sirolimus