The Parkinson's disease-associated protein DJ-1 plays a positive nonmitochondrial role in endocytosis inDictyosteliumcells

• DOI: 10.1242/dmm.028084
• Publication Date: 2017-08-18T00:10:16Z
• Authors: Suwei Chen; Sarah J. Annesley; Rasha A. F. Jasim; Vanessa J. Musco; Oana Sanislav; Paul R. Fisher
• Keywords: Multicellular organism; Pinocytosis

The loss of function DJ-1 caused by mutations causes a form familial Parkinson's Disease (PD). However, the role in healthy and PD cells is poorly understood. Even its subcellular localization mammalian uncertain, both cytosolic mitochondrial locations having been reported. We show here that normally located cytoplasm Dictyostelium discoideum cells. With unique life cycle, straightforward genotype-phenotype relationships, experimental accesibility genetic tractability, offers an attractive model to investigate roles PD-associated genes. Furthermore, study biology, genome transcription AMPK-mediated cytopathologies dysfunction have well developed this organism. Unlike systems, reproducible readily assayed array aberrant phenotypes – defective phototaxis, impaired growth, normal rates endocytosis characteristic defects multicellular morphogenesis. This makes it possible whether underlying cytopathological mechanisms involve dysfunction. has single homologue genome. By regulating expression level D. discoideum, we unstressed cells, required for endocytic nutrient uptake (phagocytosis lesser extent pinocytosis) thus growth. Reduced had no effect on phototaxis migratory “slug” stage lifecycle, but resulted thickened stalks final fruiting bodies. pattern distinct from observed result dyfunction. Direct measurement respiratory intact revealed knock down stimulates while overexpression inhibits activity. Together our results suggest positive pathways loss-of-function are not associated with function.