Properties of <i>N</i>-acetylglucosamine 1-phosphotransferase from human lymphoblasts

Little, L E; Alcouloumre, M; Drotar, A; Herman, Sheldon; Robertson, Robin; Yeh, Richard; Miller, A. T.

doi:10.1042/bj2480151

Cited by 21 publications

(19 citation statements)

References 23 publications

(13 reference statements)

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“…of the appropriate 4-methylumbelliferyl substrate at pH 4.5 and 3.7, respectively, in the presence of 0.1% Triton X-100. 66 Protein concentration was measured with the Bio-Rad dye reagent using bovine serum albumin as a standard.…”

Section: Determination Of Cathepsin Activitymentioning

confidence: 99%

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D

et al. 2003

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The role of cathepsin D in stress-induced cell death has been investigated by using ovine fibroblasts exhibiting a missense mutation in the active site of cathepsin D. The cathepsin D (lysosomal aspartic protease) deficiency did not protect cells against toxicity induced by doxorubicin and other cytotoxic agents, neither did it protect cells from caspase activation. Moreover, the cathepsin D inhibitor, pepstatin A, did not prevent stress-induced cell death in human fibroblasts or lymphoblasts. The possible role of lysosomal ceramide or sphingosine-mediated activation of cathepsin D in apoptosis was also excluded by using human cells either overexpressing or deficient in acid ceramidase. However, a normal lysosomal function seems to be required for efficient cell death, as indicated by the finding that fibroblasts from patients with mucolipidosis II were partially resistant to staurosporine, sphingosine and TNF-induced apoptosis, suggesting a key role of lysosomes in cell death.

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Section: Determination Of Cathepsin Activitymentioning

confidence: 99%

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D

et al. 2003

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“…Patients with the autosomal recessive disorder termed I-Cell Disease (ICD) have severely reduced levels of the enzyme N-acetylglucosamine 1-phosphotransferase, which forms the Man-6-P moiety on newly synthesized lysosomal enzymes (Hasilik et al, 1981;Reitman et al, 1981). Although this disorder results in severe cellular lysosomal enzyme deficiencies in many tissues, certain cell types in ICD patients, such as B lymphocytes, have nearly normal levels of lysosomal enzymes (Little et al, 1987;Okada et al, 1988;Tsuji et al, 1988). The targeting of newly synthesized lysosomal enzymes in an ICD B lymphoblastoid cell line occurs by a direct intracellular route (DiCioccio and Miller, 1991;Glickman and Kornfeld, 1993) and in at least one instance is dependent upon the selective recognition of amino acid sequences present in lysosomal enzymes but absent from related secretory proteins (Glickman and Kornfeld, 1993).…”

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confidence: 99%

The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts.

Glickman

Morton

Slot

et al. 1996

The Journal of Cell Biology

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Abstract. The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules and lysosomal hydrolases were studied in I-Cell Disease (ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC class II-invariant chain complexes colocalized with the lysosomal hydrolase cathepsin D in buds and vesicles that lacked markers of clathfin-coated vesicle-mediated transport. These vesicles fused with the endocytic pathway leading to the formation of "early" MHC class II-rich compartments (MIICs). Similar structures were observed in the TGN of normal [3 lymphoblasts although they were less abundant. Metabolic labeling and subcellular fractionation experiments indicated that newly synthesized cathepsin D and MHC class II-invariant chain complexes enter a non-clathfin-coated vesicular structure after their passage through the TGN and segregation from the secretory pathway. These vesicles were also devoid of the cation-dependent mannose 6-phosphate (Man-6-P) receptor, a marker of early and late endosomes. These findings suggest that in ICD B lymphoblasts the majority of MHC class II molecules are transported directly from the TGN to "early" MIICs and that acid hydrolases can be incorporated into MIICs simultaneously by a Man-6-P-independent process. M AJOR histocompatibility complex (MHC) 1 molecules mediate the presentation of antigenic peptides by antigen presenting cells (APCs) to T lymphocytes. Almost all cell types express MHC class I molecules, which display a variety of cytoplasmically derived peptides for presentation to CD8-positive T lymphocytes. MHC class II molecules are found on a restricted set of cell types such as B lymphocytes, macrophages, dendritic cells including epidermal Langerhans cells, and thymic epithelial cells. MHC class II molecules bind peptides generated by the proteolysis of exogenous antigens for presentation to CD4-positive T lymphocytes (reviewed in Cresswell, 1994). The MHC class II complex consists of ct and 13 chains that associate in the endoplasmic reticulum (ER) with the 31-33-kD invariant (I) chain (Marks et al., 1990). It is generally accepted that the association of I-chain with MHC class II prevents the binding of endoge-

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“…As a consequence of the I-cell defect, soluble lysosomal proteins are not phosphorylated and cannot be recognized by the Man-6-P receptor which would normally sort them into the lysosomal pathway. Previous studies have demonstrated the absence of the phosphotransferase in various cell types including lymphoid tissues of I-cell patients (Haubeck et al, 1985;Little et al, 1987;Waheed et al, 1982). However, lymphocytes as well as hepatocytes and Kuptfer cells are exceptional in I-cell disease patients in showing nearly normal levels of lysosomal enzymes (Glaser et al, 1974;Owada and Neufeld, 1982;Waheed et al, 1982), and it has been suggested that an alternative pathway exists for the delivery of proteins to lysosomes in these cell types.…”

mentioning

confidence: 99%

Granzymes A and B are targeted to the lytic granules of lymphocytes by the mannose-6-phosphate receptor.

Griffiths

Isaaz

1993

The Journal of Cell Biology

161

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Abstract. To investigate the question of whether lyric granules share a common biogenesis with lysosomes, cloned cytolytic T cell lines were derived from a patient with I-cell disease. The targeting of two soluble lyric granule components, granzymes A and B, was studied in these cells which lack a functional mannose-6-phosphate (Man-6-P) receptor-mediated pathway to lysosomes. Using antibodies and enzymatic substrates to detect the lytic proteins, I-cells were found to constitutively secrete granzymes A and B in contrast to normal cells in which these proteins were stored for regulated secretion. These results suggest that granzymes A and B are normally targeted to the lytie granules of activated lymphocytes by the Man-6-P receptor.In normal cells, the grartzymes bear Man-6-P residues, since the oligosaccharide side chains of granzymes A and B, as well as radioactive phosphate on granzyme A from labeled cells, were removed by endoglycosidase H (Endo H). However, in I-ceils, granzymes cannot bear Man-6-P and granzyme B acquires complex glycans, becoming Endo H resistant.Although the levels of granzymes A and B in cytolytic I-cell lymphocytes are <30% of the normal levels, immunolocalization and cell fractionation of granzyme A demonstrated that this reduced amount is correctly localized in the lytic granules. Therefore, a Man-6-P receptor~'ndependent pathway to the lytic granules must also exist. Cathepsin B colocalizes with granzyme A in both normal and I-cells indicating that lysosomal proteins can also use the Man-6-P receptor-independent pathway in these cells. The complete overlap of these lysosomal and lytic markers implies that the lytic granules perform both lysosomal and secretory roles in cytolytic lymphocytes. The secretory role of lytic granules formed by the Man-6-P receptor-independent pathway is intact as assessed by the ability of I-cell lymphocytes to lyse target cells by regulated secretion.

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Properties of N-acetylglucosamine 1-phosphotransferase from human lymphoblasts

Cited by 21 publications

References 23 publications

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D

Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D

The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts.

Granzymes A and B are targeted to the lytic granules of lymphocytes by the mannose-6-phosphate receptor.

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