LRRK2(I2020T) functional genetic interactors that modify eye degeneration and dopaminergic cell loss in Drosophila

Paul C. Marcogliese, Sameera Abuaish, Ghassan Kabbach, Elizabeth Abdel-Messih, Sarah Seang, Gang Li, Ruth S. Slack, M. Emdadul Haque, Katerina Venderova, David S. Park

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the primary cause for motor symptoms observed in Parkinson's disease (PD). Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most commonly linked contributor to familial PD. LRRK2 is suggested to be involved in a wide variety of cellular processes, but deciphering its role in the pathogenesis of PD has been difficult. Modelling PD in rodents has been a persistent challenge for the field. However, the fruit fly has been exploited to recapitulate PD gene related dopaminergic cell loss. Using the GAL4-UAS system and established models of hLRRK2 induced eye degeneration in Drosophila, we conducted an unbiased suppressor/enhancer screen to uncover genetic modifiers of LRRK2.We have identified 36 candidate interactors that modify LRRK2 induced toxicity in the Drosophila eye. Importantly, we determined that a subset of these interactors also modified hLRRK2(I2020T) induced dopaminergic neuronal loss in the fly brain and uncovered 16 candidates that modify dopaminergic cell loss. Our results suggest LRRK2 may be involved in a wide variety of cellular processes and the results from this screen provide an important genetic resource for further evaluation of LRRK2 function.

Original languageEnglish
Article numberddx030
Pages (from-to)1247-1257
Number of pages11
JournalHuman Molecular Genetics
Volume26
Issue number7
DOIs
Publication statusPublished - Apr 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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