title: Loss of Atg16 delays the alcohol-induced sedation response via regulation of Corazonin neuropeptide production in Drosophila.
abstract: Autophagy defects lead to the buildup of damaged proteins and organelles, reduced survival during starvation and infections, hypersensitivity to stress and toxic substances, and progressive neurodegeneration. Here we show that, surprisingly, Drosophila mutants lacking the core autophagy gene Atg16 are not only defective in autophagy but also exhibit increased resistance to the sedative effects of ethanol, unlike Atg7 or Atg3 null mutant flies. This mutant phenotype is rescued by the re-expression of Atg16 in Corazonin (Crz)-producing neurosecretory cells that are known to promote the sedation response during ethanol exposure, and RNAi knockdown of Atg16 specifically in these cells also delays the onset of ethanol-induced coma. We find that Atg16 and Crz colocalize within these neurosecretory cells, and both Crz protein and mRNA levels are decreased in Atg16 mutant flies. Thus, Atg16 promotes Crz production to ensure a proper organismal sedation response to ethanol.
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány s. 1/C, Budapest, H-1117 Hungary.|Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726 Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Varga
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány s. 1/C, 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, Pázmány s. 1/C, Budapest, H-1117 Hungary.
authors.forename: Katarina
authors.initials: K
authors.lastname: Arsikin Csordás
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány s. 1/C, Budapest, H-1117 Hungary.
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány s. 1/C, 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, Pázmány s. 1/C, Budapest, H-1117 Hungary.|Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726 Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000235:genetics*; D000071193:Autophagy-Related Protein 7 / Q000172:deficiency / Q000235:genetics; D000071183:Autophagy-Related Proteins / Q000172:deficiency / Q000235:genetics*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D009490:Neurosecretory Systems / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C000624529:Atg16 protein, Drosophila; C530193:Atg7 protein, Drosophila; D000071183:Autophagy-Related Proteins; C489221:Crz protein, Drosophila; D029721:Drosophila Proteins; D006993:Hypnotics and Sedatives; D009479:Neuropeptides; D020033:Protein Isoforms; D000431:Ethanol; D000071193:Autophagy-Related Protein 7