Leucine-rich repeat kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease

Katerina Venderova, Ghassan Kabbach, Elizabeth Abdel-Messih, Yi Zhang, Robin J. Parks, Yuzuru Imai, Stephan Gehrke, Johnny Ngsee, Matthew J. Lavoie, Ruth S. Slack, Yong Rao, Zhuohua Zhang, Bingwei Lu, M. Emdadul Haque, David S. Park

Research output: Contribution to journalArticlepeer-review

140 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4390-4404
Number of pages15
JournalHuman Molecular Genetics
Volume18
Issue number22
DOIs
Publication statusPublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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