Inhibition of Atg6 and Pi3K59F autophagy genes in neurons decreases lifespan and locomotor ability in Drosophila melanogaster.
Autophagy is a cellular mechanism implicated in the pathology of Parkinson's disease. The proteins Atg6 (Beclin 1) and Pi3K59F are involved in autophagosome formation, a key step in the initiation of autophagy. We first used the GMR-Gal4 driver to determine the effect of reducing the expression of the genes encoding these proteins on the developing Drosophila melanogaster eye. Subsequently, we inhibited their expression in D. melanogaster neurons under the direction of a Dopa decarboxylase (Ddc) transgene, and examined the effects on longevity and motor function. Decreased longevity coupled with an age-dependent loss of climbing ability was observed. In addition, we investigated the roles of these genes in the well-studied α-synuclein-induced Drosophila model of Parkinson's disease. In this context, lowered expression of Atg6 or Pi3K59F in Ddc-Gal4-expressing neurons results in decreased longevity and associated age-dependent loss of locomotor ability. Inhibition of Atg6 or Pi3K59F together with overexpression of the sole pro-survival Bcl-2 Drosophila homolog Buffy in Ddc-Gal4-expressing neurons resulted in further decrease in the survival and climbing ability of Atg6-RNAi flies, whereas these measures were ameliorated in Pi3K59F-RNAi flies.
Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
P G
PG
M'Angale
Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada bestave@mun.ca.
B E
BE
Staveley
D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1 / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D004296:Dopa Decarboxylase / Q000096:biosynthesis / Q000235:genetics*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008136:Longevity / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D051844:alpha-Synuclein / Q000235:genetics
C580769:Atg6 protein, Drosophila; D000071186:Beclin-1; D029721:Drosophila Proteins; D051844:alpha-Synuclein; D004296:Dopa Decarboxylase