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

摘要: The loss of function DJ-1 caused by mutations in DJ1 causes a form familial Parkinson's disease (PD). However, the role healthy and PD cells is poorly understood. Even its subcellular localization mammalian uncertain, with 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 accessibility genetic tractability, D.discoideum offers an attractive model to investigate roles PD-associated genes. Furthermore, study biology, genome transcription AMP-activated protein kinase-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 and, lesser extent, pinocytosis) thus growth. Reduced had no effect on phototaxis migratory 'slug' stage but resulted thickened stalks final fruiting bodies. pattern phenotypes distinct from observed result dyfunction. Direct measurement respiratory intact revealed knockdown stimulates whereas overexpression inhibits activity. Together, our results suggest positive pathways loss-of-function are not associated function.