title: Overexpression of Buffy enhances the loss of parkin and suppresses the loss of Pink1 phenotypes in Drosophila.
abstract: Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson's disease (PD). Attributed to the failure of neurons to clear dysfunctional mitochondria, loss of gene expression leads to loss of nigrostriatal neurons. The Pink1/parkin pathway plays a role in the quality control mechanism aimed at eliminating defective mitochondria, and the failure of this mechanism results in a reduced lifespan and impaired locomotor ability, among other phenotypes. Inhibition of parkin or Pink1 through the induction of stable RNAi transgene in the Ddc-Gal4-expressing neurons results in such phenotypes to model PD. To further evaluate the effects of the overexpression of the Bcl-2 homologue Buffy, we analysed lifespan and climbing ability in both parkin-RNAi- and Pink1-RNAi-expressing flies. In addition, the effect of Buffy overexpression upon parkin-induced developmental eye defects was examined through GMR-Gal4-dependent expression. Curiously, Buffy overexpression produced very different effects: the parkin-induced phenotypes were enhanced, whereas the Pink1-enhanced phenotypes were suppressed. Interestingly, the overexpression of Buffy along with the inhibition of parkin in the neuron-rich eye results in the suppression of the developmental eye defects.
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.|Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
authors.forename: P Githure
authors.initials: PG
authors.lastname: M'Angale
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.|Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Staveley
mesh_terms: D017668:Age of Onset; D000818:Animals; D002470:Cell Survival; D003470:Culture Media; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D005808:Genes, Recessive; D005838:Genotype; D008297:Male; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria; D009068:Movement; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034622:RNA Interference; D013696:Temperature; D019076:Transgenes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D003470:Culture Media; D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D044767:Ubiquitin-Protein Ligases; C477358:Buffy protein, Drosophila; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase; C487430:park protein, Drosophila
keywords: Buffy; Ddc-Gal4; GMR-Gal4; Parkinson’s disease; Pink1; maladie de Parkinson; parkin