Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The quaternary structure and binding activity of the murine 46-kDa mannose 6-phosphate receptor (46MPR) were studied in semi-intact murine cells that overexpress the murine receptor. Chemical cross-linking studies showed that the murine 46MPR exists in monomer, dimer, and tetramer forms in membranes of overexpressing murine cells. Treatment of permeabilized cells with Mn2+ increased the tetramer form of 46MPR, and this tetramerization was reversed by removal of Mn2+. Thus, the divalent cations affected the distribution of receptor among the three forms, favoring tetramerization at the expense of dimer and monomer. Low temperature (4 degrees C) also increases the fraction present as tetramer. The binding assay results show that Mn2+ is required for the 46MPR to achieve and retain the ability to bind ligand at 37 degrees C but not at 4 degrees C. Preincubation with Mn2+ produced a 3-fold increase in Man-6-P-specific binding of beta-glucuronidase which paralleled the 3-fold increase in tetramer seen during preincubation with Mn2+. The similarity of the effects of addition and removal of Mn2+ on enzyme binding to the effects of Mn2+ on favoring tetramer formation suggests that divalent cation-dependent tetramerization of the 46MPR contributes to the stimulation of ligand binding to the 46MPR by divalent cations.
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PMID:Divalent cation-dependent stimulation of ligand binding to the 46-kDa mannose 6-phosphate receptor correlates with divalent cation-dependent tetramerization. 132 39

We studied the function of the human small (46-kDa) mannose 6-phosphate receptor (SMPR) in transfected mouse L cells that do not express the larger insulin-like growth factor II/mannose 6-phosphate receptor. Cells overexpressing human SMPR were studied for enzyme binding to cell surface receptors, for binding to intracellular receptors in permeabilized cells, and for receptor-mediated endocytosis of recombinant human beta-glucuronidase. Specific binding to human SMPR in permeabilized cells showed a pH optimum between pH 6.0 and pH 6.5. Binding was significant in the presence of EDTA but was enhanced by added divalent cations. Up to 2.3% of the total functional receptor could be detected on the cell surface by enzyme binding. We present experiments showing that at very high levels of overexpression, and at pH 6.5, human SMPR mediated the endocytosis of beta-glucuronidase. At pH 7.5, the rate of endocytosis was only 14% the rate seen at pH 6.5. Cells overexpressing human SMPR also showed reduced secretion of newly synthesized beta-glucuronidase when compared to cells transfected with vector only, suggesting that overexpressed human SMPR can participate in sorting of newly synthesized beta-glucuronidase and partially correct the sorting defect in mouse L cells that do not express the insulin-like growth factor II/mannose 6-phosphate receptor.
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PMID:The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of beta-glucuronidase. 217 72