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dictyNews Volume 43 Number 19
dictyNews
Electronic Edition
Volume 43, number 19
August 18, 2017
Please submit abstracts of your papers as soon as they have been
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or by using the form at
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Abstracts
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The Parkinson's disease-associated protein DJ-1 plays a positive
nonmitochondrial role in endocytosis in Dictyostelium cells
Suwei Chen, Sarah J. Annesley, Rasha A. F. Jasim, Vanessa J. Musco,
Oana Sanislav, and Paul R. Fisher
Dis Model Mech, Posted Online August 17, 2017, doi:10.1242/dmm.028084
OPEN ACCESS ARTICLE
http://dmm.biologists.org/content/early/2017/08/16/dmm.028084
The loss of function of DJ-1 caused by mutations of DJ-1 causes a form of
familial Parkinson’s Disease (PD). However, the role of DJ-1 in healthy
and in PD cells is poorly understood. Even its subcellular localization in
mammalian cells is uncertain, both cytosolic and mitochondrial locations
having been reported. We show here that DJ-1 is normally located in the
cytoplasm in healthy Dictyostelium discoideum cells. With its unique life
cycle, straightforward genotype-phenotype relationships, experimental
accesibility and genetic tractability, Dictyostelium discoideum offers an
attractive model to investigate the roles of PD-associated genes. Furthermore,
the study of mitochondrial biology, mitochondrial genome transcription and
AMPK-mediated cytopathologies in mitochondrial dysfunction have been well
developed in this organism. Unlike mammalian systems, Dictyostelium
mitochondrial dysfunction causes a reproducible and readily assayed array of
aberrant phenotypes – defective phototaxis, impaired growth, normal rates of
endocytosis and characteristic defects in multicellular morphogenesis. This
makes it possible to study whether the underlying cytopathological mechanisms
of familial PD involve mitochondrial dysfunction. DJ-1 has a single homologue
in the Dictyostelium genome. By regulating the expression level of DJ-1 in D.
discoideum, we show here that in unstressed cells, DJ-1 is required for normal
rates of endocytic nutrient uptake (phagocytosis and to a lesser extent
pinocytosis) and thus growth. Reduced expression of DJ-1 had no effect on
phototaxis in the multicellular migratory “slug” stage of the lifecycle, but
resulted in thickened stalks in the final fruiting bodies. This pattern of
phenotypes is distinct from that observed in Dictyostelium to result from
mitochondrial dyfunction. Direct measurement of mitochondrial respiratory
function in intact cells revealed that DJ-1 knock down stimulates while DJ-1
overexpression inhibits mitochondrial activity. Together our results suggest
positive roles for DJ-1 in endocytic pathways and loss-of-function
cytopathologies that are not associated with impaired mitochondrial function.
Submitted by Paul Fisher[P.Fisher@latrobe.edu.au]
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[End dictyNews, volume 43, number 19]
