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Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases
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Sandra Pohl
Published/Copyright:
May 9, 2009
Abstract
Lysosomes contain more than 50 soluble hydrolases that are targeted to lysosomes in a mannose 6-phosphate (Man6P)-dependent manner. The phosphorylation of man- nose residues on high mannose-type oligosaccharides of newly synthesized lysosomal enzymes is catalyzed by two multimeric enzymes, GlcNAc-1-phosphotransferase and GlcNAc-1-phosphodiester-α-N-acetylglucosaminidase, allowing the binding to two distinct Man6P receptors in the Golgi apparatus. Inherited defects in the GlcNAc-1-phosphotransferase complex result in missorting and cellular loss of lysosomal enzymes, and the subsequent lysosomal dysfunction causes the lysosomal storage disorders mucolipidosis types II and III. Biosynthetic studies and the availability of Man6P receptor-deficient mouse models have provided new insights into the structural requirements for preferential binding of subsets of lysosomal enzymes to Man6P receptors as well as the identification of alternative targeting pathways.
Keywords: GlcNAc-1-phosphotransferase; lysosomal enzymes; lysosomal storage disease; mannose 6-phosphate; mannose 6-phosphate receptors; mucolipidosis
Received: 2009-2-23
Accepted: 2009-4-6
Published Online: 2009-05-09
Published in Print: 2009-07-01
©2009 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Guest Editorial
- Highlight: Perspectives in glycobiology
- Cell biology and glycosylation: protein targeting by O- and N-linked glycosylation
- Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases
- Glycosylation pattern of brush border-associated glycoproteins in enterocyte-like cells: involvement of complex-type N-glycans in apical trafficking
- Impact of glycosylation and detergent-resistant membranes on the function of intestinal sucrase-isomaltase
- MUC1 traverses apical recycling endosomes along the biosynthetic pathway in polarized MDCK cells
- Cell biology and glycosylation: carbohydrate-mediated recognition and signaling in cell proliferation and differentiation
- From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans
- Brain development needs sugar: the role of polysialic acid in controlling NCAM functions
- Beyond glycosylation: sialic acid precursors act as signaling molecules and are involved in cellular control of differentiation of PC12 cells
- Glycosylation and disease
- Management of the human mucosal defensive barrier: evidence for glycan legislation
- Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
- GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells
- Tumor-associated MUC1 glycopeptide epitopes are not subject to self-tolerance and improve responses to MUC1 peptide epitopes in MUC1 transgenic mice
- Protein-specific glycosylation and its control
- Protein-specific glycosylation: signal patches and cis-controlling peptidic elements
- O-glycosylation pattern of CD24 from mouse brain
- Advancements in analytical techniques
- Carbohydrate microarrays: key developments in glycobiology
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Keywords for this article
GlcNAc-1-phosphotransferase;
lysosomal enzymes;
lysosomal storage disease;
mannose 6-phosphate;
mannose 6-phosphate receptors;
mucolipidosis
Articles in the same Issue
- Guest Editorial
- Highlight: Perspectives in glycobiology
- Cell biology and glycosylation: protein targeting by O- and N-linked glycosylation
- Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases
- Glycosylation pattern of brush border-associated glycoproteins in enterocyte-like cells: involvement of complex-type N-glycans in apical trafficking
- Impact of glycosylation and detergent-resistant membranes on the function of intestinal sucrase-isomaltase
- MUC1 traverses apical recycling endosomes along the biosynthetic pathway in polarized MDCK cells
- Cell biology and glycosylation: carbohydrate-mediated recognition and signaling in cell proliferation and differentiation
- From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans
- Brain development needs sugar: the role of polysialic acid in controlling NCAM functions
- Beyond glycosylation: sialic acid precursors act as signaling molecules and are involved in cellular control of differentiation of PC12 cells
- Glycosylation and disease
- Management of the human mucosal defensive barrier: evidence for glycan legislation
- Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
- GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells
- Tumor-associated MUC1 glycopeptide epitopes are not subject to self-tolerance and improve responses to MUC1 peptide epitopes in MUC1 transgenic mice
- Protein-specific glycosylation and its control
- Protein-specific glycosylation: signal patches and cis-controlling peptidic elements
- O-glycosylation pattern of CD24 from mouse brain
- Advancements in analytical techniques
- Carbohydrate microarrays: key developments in glycobiology
- On-line nano-HPLC/ESI QTOF MS monitoring of α2–3 and α2–6 sialylation in granulocyte glycosphingolipidome
