ArticleBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine2011
Vesicular distribution of Secretory Pathway Ca²+-ATPase isoform 1 and a role in manganese detoxification in liver-derived polarized cells.
Article in Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Manganese: From Soil to Human Health-A Comprehensive Overview of Its Biological and Environmental Significance.Nutrients · 2024Review
- The impact of manganese on vascular endothelium.Toxicological research · 2024Review
- Insights into the regulation of cellular MnBiochimica et biophysica acta. Molecular basis of disease · 2023Article
- Cryo-EM structures of human SPCA1a reveal the mechanism of CaScience advances · 2023Article
- Primary Active CaCold Spring Harbor perspectives in biology · 2020Review
- ZIP14 is degraded in response to manganese exposure.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Genetic Disorders of Manganese Metabolism.Current neurology and neuroscience reports · 2019Review
- An N-terminal CaThe Journal of biological chemistry · 2019Article
- SLC30A10 Mutation Involved in Parkinsonism Results in Manganese Accumulation within Nanovesicles of the Golgi Apparatus.ACS chemical neuroscience · 2019Article
- Manganese-Induced Neurotoxicity: New Insights Into the Triad of Protein Misfolding, Mitochondrial Impairment, and Neuroinflammation.Frontiers in neuroscience · 2019Review
- Rab17 regulates apical delivery of hepatic transcytotic vesicles.Molecular biology of the cell · 2018Article
- Manganese transport and toxicity in polarized WIF-B hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- A Serine/Threonine Kinase 16-Based Phospho-Proteomics Screen Identifies WD Repeat Protein-1 As A Regulator Of Constitutive Secretion.Scientific reports · 2018Article
- Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin.Molecular biology of the cell · 2017Article
- Influence of iron metabolism on manganese transport and toxicity.Metallomics : integrated biometal science · 2017Review
- "Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies".BMC pharmacology & toxicology · 2016Review
- Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 Protein as a Manganese Transporter.The Journal of biological chemistry · 2016Article
- Exposure, epidemiology, and mechanism of the environmental toxicant manganese.Environmental science and pollution research international · 2016Review
- Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.Nature communications · 2016Article
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6 authors at 2 institutions in 1 country.
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Abstract
Manganese is a trace element that is an essential co-factor in many enzymes critical to diverse biological pathways. However, excess Mn(2+) leads to neurotoxicity, with psychiatric and motor dysfunction resembling parkinsonism. The liver is the main organ for Mn(2+) detoxification by excretion into bile. Although many pathways of cellular Mn(2+) uptake have been established, efflux mechanisms remain essentially undefined. In this study, we evaluated a potential role in Mn(2+) detoxification by the Secretory Pathway Ca(2+), Mn(2+)-ATPase in rat liver and a liver-derived cell model WIF-B that polarizes to distinct bile canalicular and sinusoidal domains in culture. Of two known isoforms, only secretory pathway Ca(2+)-ATPase isoform 1 (SPCA1) was expressed in liver and WIF-B cells. As previously observed in non-polarized cells, SPCA1 showed overlapping distribution with TGN38, consistent with Golgi/TGN localization. However, a prominent novel localization of SPCA1 to an endosomal population close to, but not on the basolateral membrane was also observed. This was confirmed by fractionation of rat liver homogenates which revealed dual distribution of SPCA1 to the Golgi/TGN and a fraction that included the early endosomal marker, EEA1. We suggest that this novel pool of endosomes may serve to sequester Mn(2+) as it enters from the sinusoidal/basolateral domains. Isoform-specific partial knockdown of SPCA1 delayed cell growth and formation of canalicular domain by about 30% and diminished viability upon exposure to Mn(2+). Conversely, overexpression of SPCA1 in HEK 293T cells conferred tolerance to Mn(2+) toxicity. Taken together, our findings suggest a role for SPCA1 in Mn(2+) detoxification in liver.
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