Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell interactions in the nervous system are frequently mediated by surface proteins that are attached to the membrane by a glycosyl phosphatidylinositol (GPI) anchor. In this study, we have characterized the expression of such proteins on glial cells. We have detected a major GPI-anchored protein on astrocytes and Schwann cells, with a molecular weight of 140 kD. When Schwann cells were treated with forskolin to promote a myelinating phenotype, expression of this 140-kD protein dramatically decreased, whereas another GPI-anchored protein of 80 kD was strongly induced; expression of other integral membrane proteins were likewise dramatically altered. The size and pattern of expression of the 140-kD protein suggested that it might correspond to the Ran-2 antigen, a glial lineage marker. This notion was confirmed by immunoprecipitating this 140-kD protein with the Ran-2 monoclonal antibody. The Ran-2 antigen is expressed over the entire Schwann cell surface in a punctate fashion; it is removed by phosphatidylinositol phospholipase C treatment, thereby confirming that it is GPI-anchored. When Schwann cells are cocultured with neurons, the Ran-2 antigen initially concentrates at sites of Schwann cell contact with neurons, suggesting that it may play a role in early Schwann cell-neuron interactions; it is then downregulated. Protein sequencing of the Ran-2 antigen immunopurified from rat brain membranes showed complete identity over two extended segments with the copper binding protein ceruloplasmin. These findings indicate that astrocytes and Schwann cells express a novel GPI-anchored form of ceruloplasmin and suggest that this GPI form plays a role in axonal-glial interactions.
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PMID:Ran-2, a glial lineage marker, is a GPI-anchored form of ceruloplasmin. 978 74

Ceruloplasmin (Cp), a multicopper ferroxidase, is expressed as both a secreted (sCp) plasma enzyme from the liver and a membrane-bound glycosylphosphatidylinositol-anchored (GPI-Cp) splice variant protein. Cp is thought to be essential for iron mobilization as selective iron overload occurs in aceruloplasminemia in humans and in Cp null mice. Dietary copper-deficient (CuD) rodents have near total loss of Cp activity, severe loss of Cp protein and develop anemia. Hepatic iron augmentation is often observed, suggesting that loss of Cp function may be correlated with anemia. The impact of CuD treatment on GPI-Cp has not previously been evaluated. Our hypothesis was that CuD rodents would have lower levels of GPI-Cp and this would correlate with higher tissue iron retention. In these studies, GPI-Cp was detected in purified membranes of multiple organs of rats and mice but not Cp -/- mice. Immunoreactive Cp protein was released with phosphatidylinositol phospholipase C treatment and expressed ferroxidase activity. Following perinatal and postnatal copper restriction, GPI-Cp was markedly lower in the spleen and modestly lower in the liver of CuD rats and mice, when compared with copper-adequate (CuA) rodents. However, spleen non-heme iron (NHI) was lower in CuD than CuA rats, and not different in CuD mice. Hepatic iron was higher only in CuD mice. Spleen and liver membranes of CuD rats expressed augmented levels of ferroportin, the iron efflux transporter, which may explain lower NHI content in the spleen of CuD rats despite a greater than 50% lower level of the multicopper ferroxidase GPI-Cp. Spleen and liver levels of GPI-Cp mRNA were not impacted in CuD rats, suggesting that turnover rather than biosynthesis may explain the lower steady-state levels of GPI-Cp following dietary copper restriction. Lower GPI-Cp did not correlate with tissue iron retention and thus the role, if any, of Cp in anemia of copper deficiency is unknown.
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PMID:Glycosylphosphatidylinositol-linked ceruloplasmin is expressed in multiple rodent organs and is lower following dietary copper deficiency. 2135 16