Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin

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Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin

Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1-induced cell death via down-regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi and causes GPP130 to oligomerize/aggregate, and the complexes are diverted to lysosomes. In fact, based on experiments using the self-int...

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Manganese-induced Trafficking and Turnover of the cis-Golgi Glycoprotein GPP130

Manganese is an essential element that is also neurotoxic at elevated exposure. However, mechanisms regulating Mn homeostasis in mammalian cells are largely unknown. Because increases in cytosolic Mn induce rapid changes in the localization of proteins involved in regulating intracellular Mn concentrations in yeast, we were intrigued to discover that low concentrations of extracellular Mn induc...

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The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin.

Most soluble lysosomal proteins bind the mannose 6-phosphate receptor (M6P-R) to be sorted to the lysosomes. However, the lysosomes of I-cell disease (ICD) patients, a condition resulting from a mutation in the phosphotransferase that adds mannose 6-phosphate to hydrolases, have near normal levels of several lysosomal proteins, including the sphingolipid activator proteins (SAPs), GM2AP and pro...

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................................................................................................................................. 4 ACKNOWLEDGEMENTS .......................................................................................................... 6 INTRODUCTION ........................................................................................................................ 8 1.1...

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Disruption of astrocytic glutamine turnover by manganese is mediated by the protein kinase C pathway.

Manganese (Mn) is a trace element essential for normal human development and is required for the proper functioning of a variety of physiological processes. Chronic exposure to Mn can cause manganism, a neurodegenerative disorder resembling idiopathic Parkinson's disease (PD). Mn(II) neurotoxicity is characterized by astrocytic impairment both in the expression and activity of glutamine (Gln) t...

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ژورنال

عنوان ژورنال: Molecular Biology of the Cell

سال: 2017

ISSN: 1059-1524,1939-4586

DOI: 10.1091/mbc.e17-05-0326