title: Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease.
abstract: Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human LRRK2 (mutations in kinase, COR or LRR domains, resp.). Ectopic expression of WT or mutant LRRK2 in dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes in locomotor activity. Overall, the ubiquitous expression of LRRK2 increased lifespan and fertility of the flies. However, these flies were more sensitive to rotenone. LRRK2 expression in the eye exacerbated retinal degeneration. Importantly, in double transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.
authors.affiliation: Ottawa Health Research Institute, Neuroscience Research Institute, Ontario, Canada.
authors.forename: Katerina
authors.initials: K
authors.lastname: Venderova
authors.forename: Ghassan
authors.initials: G
authors.lastname: Kabbach
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Abdel-Messih
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Parks
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Imai
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehrke
authors.forename: Johnny
authors.initials: J
authors.lastname: Ngsee
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lavoie
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Slack
authors.forename: Yong
authors.initials: Y
authors.lastname: Rao
authors.forename: Zhuohua
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bingwei
authors.initials: B
authors.lastname: Lu
authors.forename: M Emdadul
authors.initials: ME
authors.lastname: Haque
authors.forename: David S
authors.initials: DS
authors.lastname: Park
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008017:Life Expectancy; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human