Absence of pretaporter restrains features of the parkin phenotype in Drosophila.

Background: Scientific research based on model organisms can help to understand the biology of Parkinson's Disease, the second most prevalent neurodegenerative disease. Drosophila melanogaster mutant for the gene parkin, homologous to human's PARK2, exhibit well-characterized phenotypes including loss of dopaminergic neurons, lower survival and motor defects. Through the transcriptomic analysis of an exceptional case of reversible neurodegeneration in Drosophila, our group identified that the gene pretaporter, homologous to TXNDC5 of humans, was downregulated in the reversal phase. Here, we explore the hypothesis that the lack of expression of pretaporter will restrain phenotypes observed in Drosophila parkin mutants.

Methods: After establishing by immunochemistry that Pretaporter is expressed in PPL1 dopaminergic neurons, we constructed pretaporter-parkin double mutants flies to investigate the hypothesis through immunohistochemistry, survival and climbing assays.

Conclusions: It was found that the loss-of-function mutation in pretaporter significatively restrains the phenotype caused by the loss-of-function mutation in parkin in several key aspects: it abolished the loss of PPL1 neurons normally seen in parkin mutant flies, promoted their survival in both sexes and reduced the decay in motor ability in parkin female flies. We propose that the absence of Pretaporter in parkin mutant flies prevents the death of dopaminergic neurons by rendering them resistant to Draper-mediated-phagocytosis.