Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of β-Galactosidase, Cathepsin A, and Neuraminidase

Pshezhetsky, Alexey V.; Potier, Michel

doi:10.1074/jbc.271.45.28359

Cited by 85 publications

(94 citation statements)

References 26 publications

(20 reference statements)

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“…In the lysosome, sialidase is associated with lysosomal carboxypeptidase A (also cathepsin A or protective protein), ␤-galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a multienzyme complex (1)(2)(3). Dissociation of the complex in vitro results in complete inactivation of sialidase, although activity can be restored after the reconstitution of the complex (2).…”

Section: Results In Inhibition Of Sialidase Internalization In Activamentioning

confidence: 99%

Intracellular Distribution of Lysosomal Sialidase Is Controlled by the Internalization Signal in Its Cytoplasmic Tail

Lukong¹,

Seyrantepe²,

Landry³

et al. 2001

Journal of Biological Chemistry

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Sialidase (neuraminidase), encoded by the neu-1 gene in the major histocompatibility complex locus catalyzes the intralysosomal degradation of sialylated glycoconjugates. Inherited deficiency of sialidase results in sialidosis or galactosialidosis, both severe metabolic disorders associated with lysosomal storage of oligosaccharides and glycopeptides. Sialidase also plays an important role in cellular signaling and is specifically required for the production of cytokine interleukin-4 by activated T lymphocytes. In these cells, neu-1-encoded sialidase activity is increased on the cell surface, suggesting that a specific mechanism regulates sorting of this enzyme to the plasma membrane. We investigated that mechanism by first showing that sialidase contains the internalization signal found in lysosomal membrane proteins targeted to endosomes via clathrin-coated pits.

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Section: Results In Inhibition Of Sialidase Internalization In Activamentioning

confidence: 99%

Intracellular Distribution of Lysosomal Sialidase Is Controlled by the Internalization Signal in Its Cytoplasmic Tail

Lukong¹,

Seyrantepe²,

Landry³

et al. 2001

Journal of Biological Chemistry

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“…To study the effect of exogenous mouse Neu1 on phagocytosis of IgG-opsonized beads, the cells were pretreated overnight by the medium supplemented with Neu1 (1 milliunits/ml of medium) isolated from mouse kidney tissue by the affinity chromatography on concanavalin A and p-aminophenyl-␤-D-thiogalactopyranoside-agarose (Sigma) columns as previously described (26). The cells were washed twice with culture medium, and the assay proceeded as described above.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Phagocytosis in Macrophages by Neuraminidase 1

Seyrantepe

Iannello

Liang

et al. 2010

Journal of Biological Chemistry

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The differentiation of monocytes into macrophages and dendritic cells is accompanied by induction of cell-surface neuraminidase 1 (Neu1) and cathepsin A (CathA), the latter forming a complex with and activating Neu1. To clarify the biological importance of this phenomenon we have developed the gene-targeted mouse models of a CathA deficiency (CathA S190A ) and a double CathA/Neu1 deficiency (CathA S190A-Neo ). Macrophages of CathA S190A-Neo mice and their immature dendritic cells showed a significantly reduced capacity to engulf Grampositive and Gram-negative bacteria and positively and negatively charged polymer beads as well as IgG-opsonized beads and erythrocytes. Properties of the cells derived from CathA S190A mice were indistinguishable from those of wild-type controls, suggesting that the absence of Neu1, which results in the increased sialylation of the cell surface proteins, probably affects multiple receptors for phagocytosis. Previous data showed that mammalian neuraminidase 1 (Neu1), 5 in addition to its role in the intralysosomal catabolism, may be also involved in cellular signaling during the immune response. In particular, during the activation of mouse T cells, Neu1 is expressed on the plasma membrane and is required for the early production of interleukin-4 and for the interaction of T cells with the antigen-presenting cells (8 -12). In addition, Neu1 of T cells converts the group-specific component (Gc protein) into a factor necessary for the inflammation-primed activation of macrophages (13,14). T cells derived from SM/J or B10.SM strains of mice with the reduced Neu1 activity, due to a missense mutation in the Neu1 gene (15), fail to convert Gc and synthesize interleukin-4, whereas B cells of these mice cannot produce IgG 1 and IgE after immunization with pertussis toxin (8,14,16). Strikingly, surface desialylation of macrophages by viral sialidase from Arthrobacter ureafaciens significantly increases their capacity for phagocytosis of influenza virus-infected HeLa cells (17), providing the direct link between the surface sialylation of antigen-presenting cells and their biological activity.Previously we showed that Neu1 increased 14-fold during the differentiation of human monocytes into macrophages (18). * This work was supported in part by Canadian Institutes of Health ResearchOperating Grants MOP 15079 and GOP 38107 and by an equipment grant from Canadian Foundation for Innovation (to A. V. P.

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“…Lysosomal enzymes bhexosaminidase and b-galactosidase were assayed using the corresponding fluorogenic 4-methylumbelliferyl (Muf)-glycoside derivatives as substrates. 41 Detection of ubiquitinated proteins by Western blotting. Cultured cells from LSD patients, and normal controls as well as control cells treated with 0.5 mM E-64 for 24-48 h were harvested and homogenized in boiling Laemmli buffer.…”

Section: Methodsmentioning

confidence: 99%

Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway

et al. 2006

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By comparing mRNA profiles in cultured fibroblasts from patients affected with lysosomal storage diseases, we identified differentially expressed genes common to these conditions. These studies, confirmed by biochemical experiments, demonstrated that lysosomal storage is associated with downregulation of ubiquitin C-terminal hydrolase, UCH-L1 in the cells of eight different lysosomal disorders, as well as in the brain of a mouse model of Sandhoff disease. Induction of lysosomal storage by the cysteine protease inhibitor E-64 also reduced UCH-L1 mRNA, protein level and activity. All cells exhibiting lysosomal storage contained ubiquitinated protein aggregates and showed reduced levels of free ubiquitin and decreased proteasome activity. The caspase-mediated apoptosis in E-64-treated fibroblasts was reversed by transfection with a UCH-L1 plasmid, and increased after downregulation of UCH-L1 by siRNA, suggesting that UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway can contribute to the increased cell death observed in many lysosomal storage disorders.

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Association of N-Acetylgalactosamine-6-sulfate Sulfatase with the Multienzyme Lysosomal Complex of β-Galactosidase, Cathepsin A, and Neuraminidase

Cited by 85 publications

References 26 publications

Intracellular Distribution of Lysosomal Sialidase Is Controlled by the Internalization Signal in Its Cytoplasmic Tail

Intracellular Distribution of Lysosomal Sialidase Is Controlled by the Internalization Signal in Its Cytoplasmic Tail

Regulation of Phagocytosis in Macrophages by Neuraminidase 1

Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway

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