Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.37 (CNPase)
 539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated ferritin binding is specific to white matter in mouse and human brain tissue and is not found within Multiple Sclerotic plaques. These results suggest that ferritin receptors are selectively expressed on oligodendrocytes. The present studies were designed to test the hypothesis that oligodendrocyte progenitor cells selectively bind ferritin and internalize it by methods consistent with receptor-mediated endocytosis. Using a cell culture system enriched for oligodendrocyte progenitor cells, we determined, that oligodendrocyte progenitor cells bind ferritin in a saturable and competitive manner with a K(d) of 5 nM and a receptor density of 0.06 fmol bound/20,000 cells. FITC tagged ferritin is internalized by A2B5, O4 or CNPase expressing cells in the culture, but not by GFAP+ cells. The uptake of ferritin into the oligodendrocyte progenitors was inhibited by treating the cells with inhibitors of receptor mediated endocytosis (hypertonic medium, potassium deficient medium, ATP depletion, sulfhydryl reagents). In addition exogenous ferritin decreased iron responsive element/iron regulatory protein binding indicating that the iron within the internalized ferritin is released and contributes to the intracellular iron pool. Given the relatively high amount of iron that can be delivered via ferritin, and the selective distribution of ferritin receptors in the white matter tracts in vivo, we propose that ferritin is a major source of iron for oligodendrocytes.
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PMID:Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. 1086 99

Potassium-chloride cotransporters (KCCs) collectively play a crucial role in the function and development of both the peripheral and central nervous systems. KCC4 is perhaps the least abundant KCC in the adult mammalian brain, where its localization is unknown. In the embryonic brain, KCC4 mRNA is found in the periventricular zone, cranial nerves and choroid plexus [Eur J Neurosci 16 (2002) 2358]. To investigate the distribution of KCC4 protein in the nervous system we developed a rabbit polyclonal antibody directed against a short N-terminal peptide. Western blot analysis of brain microsomal protein using purified antibody revealed the presence of a band at approximately 145 kDa, consistent with the size of a glycosylated K-Cl cotransporter. Western blot analysis of brain, spinal cord and peripheral nerves revealed high expression levels in peripheral nerves and spinal cord, with low levels in whole brain. Within the brain, the cerebral cortex, hippocampus, and cerebellum revealed minimal KCC4 expression, whereas midbrain and brainstem demonstrated higher levels. In the adult mouse brain, KCC4 staining was observed on the apical membrane of choroid plexus epithelial cells as well as in cranial nerves. All other brain structures, e.g. cortex, hippocampus, cerebellum showed no KCC4 immunoreactivity, suggesting very low or absent expression of the cotransporter in these regions. Co-staining of KCC4 with anti-MAP2, GFAP and CNPase revealed that KCC4 is expressed in peripheral neurons. Thus, KCC4 is expressed on the apical membrane of the choroid plexus, where it likely participates to K(+) reabsorption. KCC4 is also expressed in peripheral neurons, where its function remains to be determined.
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PMID:Localization of the KCC4 potassium-chloride cotransporter in the nervous system. 1469 46