Overexpression of human Atp13a2Isoform-1 protein protects cells against manganese and starvation-induced toxicity

PloS One
Janet UgolinoMervyn J Monteiro

Abstract

Mutations in ATP13A2 cause Kufor-Rakeb syndrome (KRS), a juvenile form of Parkinson's disease (PD) with dementia. However, the mechanisms by which mutations in ATP13A2 cause KRS is not understood. The mutations lead to misfolding of the translated Atp13a2 protein and its premature degradation in the endoplasmic reticulum, never reaching the lysosome where the protein is thought to function. Atp13a2 is a P-type ATPase, a class of proteins that function in ion transport. Indeed, studies of human, mouse, and yeast Atp13a2 proteins suggest a possible involvement in regulation of heavy metal toxicity. Here we report on the cytoprotective function of Atp13a2 on HeLa cells and dopamine neurons of Caenorhabditis elegans (C. elegans). HeLa cells stably overexpressing V5- tagged Atp13a2Isoform-1 protein were more resistant to elevated manganese exposure and to starvation-induced cell death compared to cells not overexpressing the protein. Because PD is characterized by loss of dopamine neurons, we generated transgenic C. elegans expressing GFP-tagged human Atp13a2 protein in dopamine neurons. The transgenic animals exhibited higher resistance to dopamine neuron degeneration after acute exposure to manganese compared to nematodes that exp...Continue Reading

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Citations

Jun 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Josephine J WuMervyn J Monteiro
Oct 13, 2020·Frontiers in Neuroscience·Dong-Ying Yan, Bin Xu
Oct 9, 2020·Acta Neuropathologica Communications·Shaoteng WangMervyn J Monteiro

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BETA
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fluorescence microscopy
transfection

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Excel
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Simple PCI
Mac
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