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Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin-like growth factor-II/mannose-6-phosphate receptor binds two classes of ligands, IGF-II and lysosomal enzymes containing the mannose-6-phosphate recognition marker. To study the interaction of the two classes of ligands at the receptor level, we have isolated 'high uptake' forms of lysosomal enzymes containing mannose-6-phosphate that had been radiolabeled biosynthetically using a tissue culture model: Tay-Sachs disease fibroblasts were incubated in medium containing [3H]mannose, ammonium chloride and mannose-6-phosphate. Under the conditions of these experiments, the Tay-Sachs disease fibroblasts synthesized and secreted radiolabeled hexosaminidase B, as confirmed by measuring enzymatic activity of cell-conditioned medium. The enzyme secreted was recognized by antibodies raised against purified hexosaminidase A and B but not by nonimmune control sera in Western blotting and immunoprecipitation experiments. The radiolabeled cell-conditioned medium was partially purified by ion-exchange chromatography on a DEAE-Sephadex column. When partially purified [3H]hexosaminidase B was incubated with rat C6 glial cells which express large numbers of IGF-II/mannose-6-phosphate receptors, the enzyme was taken up specifically via the IGF-II/mannose-6-phosphate receptor as evidenced by carbohydrate competition experiments. The specific uptake of the radiolabeled lysosomal enzyme was partially inhibited by IGF-II and an antibody against the IGF-II/mannose-6-phosphate receptor (No. 3637). We conclude that the cellular uptake of a biosynthetically labeled lysosomal enzyme, hexosaminidase B, is partially inhibited by IGF-II. We hypothesize that IGF-II might be capable of modulating lysosomal pathways in vivo.
Mol Cell Endocrinol 1992 Dec
PMID:Biosynthetic labeling of beta-hexosaminidase B: inhibition of the cellular uptake of lysosomal secretions containing [3H]hexosaminidase B by insulin-like growth factor-II in rat C6 glial cells. 130 95

Human lysosomal alpha-galactosidase A (alpha-Gal A) was stably overexpressed in CHO cells and its biosynthesis and targeting were investigated. Clone AGA5.3-1000Mx, which was the highest enzyme overexpressor, produced intracellular alpha-Gal A levels of 20,900 U/mg (approximately 100 micrograms of enzyme/10(7) cells) and secreted approximately 13,000 U (or 75 micrograms/10(7) cells) per day. Ultrastructural examination of these cells revealed numerous 0.25-1.5 microns crystalline structures in dilated trans-Golgi network (TGN) and in lysosomes which stained with immunogold particles using affinity-purified anti-human alpha-Gal A antibodies. Pulse-chase studies revealed that approximately 65% of the total enzyme synthesized was secreted, while endogenous CHO lysosomal enzymes were not, indicating that the alpha-Gal A secretion was specific. The recombinant intracellular and secreted enzyme forms were normally processed and phosphorylated; the secreted enzyme had mannose-6-phosphate moieties and bound the immobilized 215-kD mannose-6-phosphate receptor (M6PR). Thus, the overexpressed enzyme's selective secretion did not result from oversaturation of the M6PR-mediated pathway or abnormal binding to the M6PR. Of note, the secreted alpha-Gal A was sulfated and the percent of enzyme sulfation decreased with increasing amplification, presumably due to the inaccessibility of the enzyme's tyrosine residues for the sulfotransferase in the TGN. Overexpression of human lysosomal alpha-N-acetylgalactosaminidase and acid sphingomyelinase in CHO cell lines also resulted in their respective selective secretion. In vitro studies revealed that purified secreted alpha-Gal A was precipitated as a function of enzyme concentration and pH, with 30% of the soluble enzyme being precipitated when 10 mg/ml of enzyme was incubated at pH 5.0. Thus, it is hypothesized that these overexpressed lysosomal enzymes are normally modified until they reach the TGN where the more acidic environment of this compartment causes the formation of soluble and particulate enzyme aggregates. A significant proportion of these enzyme aggregates are unable to bind the M6PR and are selectively secreted via the constitutive secretory pathway, while endogenous lysosomal enzymes bind the M6PRs and are transported to lysosomes.
J Cell Biol 1992 Dec
PMID:Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion. 133 79

By using an organ culture technique, corneal endothelial cells in human embryonic eyes could be stimulated to initiate DNA synthesis by exposure to insulin like growth factor II (IGF-II). The thymidine-labelling index doubled after IGF-II supplementation. However, this stimulatory effect was neither augmented nor abrogated by the simultaneous addition of Mannose-6-Phosphate. Nor did Mannose-6-phosphate stimulate DNA synthesis in the absence of IGF II. In contrast, the IGF II effect was partly counteracted by addition of an antibody that blocks binding to the IGF type I receptor. Taken together, this data suggests that IGF II stimulates DNA-synthesis in corneal endothelium by binding to the IGF type I rather than the IGF type II/ mannose-6-phosphate receptor.
Cell Biol Int Rep 1991 Dec
PMID:Stimulatory effect of insulin like growth factor II on DNA synthesis in the human embryonic cornea. 166 38

The intraovarian insulin-like growth factor (IGF) system constitutes a triad composed of ligands, receptors, and binding proteins. Although conventional radioligand receptor assays have documented the presence of specific receptors for insulin and insulin-like peptides in some rat somatic ovarian cell types, the exact cellular localization and hormonal regulation of the receptors in question remain matters of inquiry. To reevaluate the very presence, cellular localization, and hormonal regulation of the IGF receptor gene family in the rat ovary, solution hybridization/RNase protection assays were used wherein ovarian total RNA (20 micrograms) from immature (21-23 days old) rats was hybridized with 32P-labeled type I IGF receptor, type II IGF/mannose-6-phosphate receptor, and insulin receptor riboprobes. Single protected fragments 261 (type I IGF receptor), 500 (type II IGF/mannose-6-phosphate receptor), and 478 (insulin receptor) bases long were evident in whole ovary, granulosa, and theca-interstitial cells. Hypophysectomy of immature rats led to significant (P less than 0.05) albeit variable decrements in the relative (densitometrically quantified) ovarian abundance of transcripts corresponding to the type I IGF (but not insulin or type II IGF/mannose-6-phosphate) receptor. Treatment of immature hypophysectomized rats with FSH (10 micrograms/rat.day x 2.5 days) resulted in a significant (P less than 0.05) increase (4-fold) in transcripts corresponding to the type I IGF receptor in both whole ovarian material and freshly isolated granulosa cells. Similar (3.7-fold) increments (P less than 0.05) were noted after treatment with a diethylstilbestrol-containing sc silastic implant applied for a total of 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Dec
PMID:Insulin-like growth factor receptor gene expression in the rat ovary: divergent regulation of distinct receptor species. 172 86

Cytolytic lymphocytes contain specialized lytic granules whose secretion during cell-mediated cytolysis results in target cell death. Using serial section EM of RNK-16, a natural killer cell line, we show that there are structurally distinct types of granules. Each type is composed of varying proportions of a dense core domain and a multivesicular cortical domain. The dense core domains contain secretory proteins thought to play a role in cytolysis, including cytolysin and chondroitin sulfate proteoglycan. In contrast, the multivesicular domains contain lysosomal proteins, including acid phosphatase, alpha-glucosidase, cathepsin D, and LGP-120. In addition to their protein content, the lytic granules have other properties in common with lysosomes. The multivesicular regions of the granules have an acidic pH, comparable to that of endosomes and lysosomes. The granules take up exogenous cationized ferritin with lysosome-like kinetics, and this uptake is blocked by weak bases and low temperature. The multivesicular domains of the granules are rich in the 270-kD mannose-6-phosphate receptor, a marker which is absent from mature lysosomes but present in earlier endocytic compartments. Thus, the natural killer granules represent an unusual dual-function organelle, where a regulated secretory compartment, the dense core, is contained within a pre-lysosomal compartment, the multivesicular domain.
J Cell Biol 1990 Dec
PMID:The lytic granules of natural killer cells are dual-function organelles combining secretory and pre-lysosomal compartments. 227 62

Electron microscopic approaches have been used to study the endocytic pathways from the apical and basolateral surface domains of the polarized epithelial cell, MDCK strain I, grown on polycarbonate filters. The cells were incubated at 37 degrees C in the presence of two distinguishable markers administered separately to the apical or the basolateral domain. Initially each marker was visualized within distinct apical or basolateral peripheral endosomes. However, after 15 min at 37 degrees C, both markers were observed within common perinuclear structures. The compartment in which meeting first occurred was shown to be a late endosome (prelysosome) that labeled extensively with antibodies against the cation-independent mannose-6-phosphate receptor (MPR) on cryosections. With increasing incubation times, markers passed from these MPR-positive structures into a common set of MPR-negative lysosomes that were mainly located in the apical half of the cell. A detailed quantitative analysis of the endocytic pathways was carried out using stereological techniques in conjunction with horseradish peroxidase and acid phosphatase cytochemistry. This enabled us to estimate the absolute volumes and membrane surface areas of the endocytic organelles involved in apical and basolateral endocytosis.
J Cell Biol 1989 Dec
PMID:Meeting of the apical and basolateral endocytic pathways of the Madin-Darby canine kidney cell in late endosomes. 255 51

Recently, the sequence of the human receptor for insulin-like growth factor II (IGF-II) was found to be 80% identical [Morgan et al., (1987) Nature 329, 301-307] to the sequence of a partial clone of the bovine cation-independent mannose-6-phosphate receptor [Lobel et al., (1987) Proc. Natl. Acad. Sci. USA 84, 2233-2237]. In the present study, the purified receptor for insulin-like growth factor II (IGF-II) was found to react with two different polyclonal antibodies to the purified mannose-6-phosphate receptor. Moreover, mannose-6-phosphate was found to stimulate the binding of labeled IGF-II to the IGF-II receptor by two-fold. This effect had the same specificity and affinity as the reported binding of mannose-6-phosphate to its receptor; mannose-1-phosphate and mannose had no effect on the binding of labeled IGF-II to its receptor, and the half-maximally effective concentration of mannose-6-phosphate was 0.3 mM. Also, mannose-6-phosphate did not affect labeled IGF-II binding to the insulin receptor. These results support the hypothesis that a single protein of Mr-250,000 binds both IGF-II and mannose-6-phosphate. Furthermore, they indicate that mannose-6-phosphate can modulate the interaction of IGF-II to its receptor.
Biochem Biophys Res Commun 1987 Dec 16
PMID:Interactions of the receptor for insulin-like growth factor II with mannose-6-phosphate and antibodies to the mannose-6-phosphate receptor. 296 76

Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein concentration suggesting a renotropic function in diabetic kidney growth. In order to further examine the possible involvement of the insulin-like growth factor system in initial diabetic kidney growth, we have studied the expression of the kidney insulin-like growth factor II/mannose-6-phosphate receptor during the first 4 days after induction of diabetes in rats. Using a specific antiserum (#3637) raised against the insulin-like growth factor II/mannose-6-phosphate receptor of rat chondrosarcoma a specific band with an apparent molecular weight of 220 kDa was identified in Western blotting experiments with kidney and liver protein extracts. In untreated diabetic rats a transient increase of the kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration was measured 24-48 h after the induction of diabetes (mean increase in kidney 140% and liver 112%, n = 5). This increase was followed by a subsequent decrease in the insulin-like growth factor II/mannose-6-phosphate receptor protein concentration after 3-4 days of diabetes. Insulin treatment prevented the rise both in kidney and liver tissue. Kidney weight in untreated diabetic rats increased by 25% after 4 days. In conclusion, the present study shows a transient increase of insulin-like growth factor II/mannose-6-phosphate receptor concentration in hypertrophying diabetic kidneys and in diabetic livers, contemporarily with the previously described increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein content.(ABSTRACT TRUNCATED AT 250 WORDS)
Growth Regul 1994 Dec
PMID:Increased kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration in experimental diabetes in rats. 775 75

Seminal plasma derived factors are implicated in mediating inflammation in the female reproductive tract following insemination at mating. During inflammation, leukocytes are activated to express adhesion receptors resulting in adherence to each other and for the ECM as well as for various cell types. The present study describes the purification of a leukocyte cell-cell adhesion regulator derived from seminal vesicle fluid. Seminal vesicle fluid proteins were chromatographed by cation exchange, hydrophobic interaction and reversed phase. Chromatography on Phenyl Superose resolved two distinct forms of cell-cell adhesion regulation, type I and II. Reversed phase chromatography of fractions inducing type I adhesion resulted in the isolation of a 15kDa adhesion inducing protein (pAIF-1). The N-terminal sequence contained a hydrophobic consensus sequence which exists in: two bovine seminal vesicle proteins (BSPA3, PDC 109); IGF-II receptor; fibronectin; and the cation independent mannose-6-phosphate receptor.
Biochem Biophys Res Commun 1994 Dec 15
PMID:Purification of a cell-cell adhesion regulator from porcine seminal vesicle fluid. 780 52

Chediak-Higashi Syndrome (CHS) is an autosomal recessive disease affecting secretory granules and lysosomes-like organelles. In CHS fibroblasts, acidic organelles are abnormally large and clustered in the perinuclear area. We have analyzed fibroblast cell lines from a CHS patient and from the murine model for CHS, the beige mouse, to determine which lysosome-like compartments are affected. Uptake of neutral red showed that in both beige and CHS cell lines, the acidic organelles were markedly clustered in the perinuclear region of the cells. Giant organelles (> 4 microns) were observed in a fraction of the cells, and these were more dramatic in the beige fibroblasts than in the CHS fibroblasts. The total dye uptake of both mutant cell lines was similar to their respective wild type fibroblasts, suggesting that the overall volume of acidic compartments is unaffected by the disorder. Histochemistry and immunofluorescence showed that the giant organelles in both beige and CHS fibroblasts were positive for cathepsin D, lysosome-associated membrane protein (LAMP) 1, LAMP 2, and a 120-kD lysosomal glycoprotein, all marker proteins for late endosomes and lysosomes. The giant organelles were also negative for transferrin receptor and mannose-6-phosphate receptor, and most of them were also negative for rab 7. This distribution of marker proteins shows that the giant organelles in both beige and CHS are derived from late compartments of the endocytic pathway. This conclusion was confirmed using endocytic tracers. BSA was transported to the giant organelles, but only after long incubation times, and only at 37 degrees C. alpha 2-Macroglobulin was taken up and degraded at similar rates by CHS or beige cells and their respective wild type control cells. Taken together, our results indicate that the mutation in CHS specifically affects late endosomes and lysosomes, with little or no effect on early endosomes. Although the mutation clearly causes mislocalization of these organelles, it appears to have little effect on their endocytic and degradative functions.
J Exp Med 1993 Dec 01
PMID:The giant organelles in beige and Chediak-Higashi fibroblasts are derived from late endosomes and mature lysosomes. 790 7


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