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Topology and Regulation of Ganglioside Metabolism — Function and Pathobiochemistry of Sphingolipid Activator Proteins

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Glyco-and Cellbiology

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Abstract

Glycosphingolipids (GSL) are amphiphilic plasma membrane components characteristic of vertebrate tissues (Svennerholm 1984; Ledeen and Yu 1982; van Echten and Sandhoff 1989).

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References

  • Barranger YA, Ginns EJ (1989) Glucosylceramide lipidosis: Gaucher Disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic bases of inherited disease. 6th ed. vol. II, Mc Graw-Hill, New York, pp 1677–1698

    Google Scholar 

  • Berent SL, Radin NS (1981) Mechanism of activation of glucocerebrosidase by co-β-glucosi- dase (glucosidase activator protein). Biochim Biophys Acta 664: 572–582

    PubMed  CAS  Google Scholar 

  • O’Brien JS, Kretz KA, Dewji N, Wenger DA, Esch F, Fluharty AL (1988) Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus. Science 241:1098–1101

    Article  PubMed  Google Scholar 

  • O’Brien JS (1989) β-Galactosidase deficiency (GM1, gangliosidosis, galactosialidosis, and Morquio Syndrome Type B); ganglioside sialidase deficiency (Mucolipidosis (IV). In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic bases of inherited disease 6th ed., vol. II., Mc Graw-Hill, New York, pp 1797–1806

    Google Scholar 

  • Coste H, Martel M-B, Got R (1986) Topology of glusosylceramide synthesis in Golgi membranes from porcine submaxillary glands. Biochim Biophys Acta 858:6–12

    Article  PubMed  CAS  Google Scholar 

  • Deutscher SL, Hirschberg CB (1986) Mechanism of galactosylation in the Golgi apparatus. J Biol Chem 261:96–100

    PubMed  CAS  Google Scholar 

  • Fishman PH, Brady RO (1976) Biosynthesis and function of gangliosides. Science 194:906–915

    Article  PubMed  CAS  Google Scholar 

  • Fürst W, Sandhoff K (1992) Activator proteins and topology of lysosomal sphingolipid catabo- lism. Biochim Biophys Acta 1126:1–16

    PubMed  Google Scholar 

  • Griffiths G, Hoflack B, Simons K, Mellman I, Kornfeld S (1988) The mannose-6-phosphate receptor and the biogenesis of lysosomes. Cell 52:329–341

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto Y, Suzuki A, Yamakawa T, Miyashita N, Moriwaki K (1983) Expression of GM1 and GDI a in mouse liver is linked to the H2 complex on chromosome 17. J Biochem 94:2043–2048

    PubMed  CAS  Google Scholar 

  • Ho MW, Light ND (1973) Glucocerebrosidase: reconstitution from macromolecular components depends on acidic phospholipids. Biochem J 136:821–823

    PubMed  CAS  Google Scholar 

  • Ho MW (1975) Specificity of low molecular weight glycoprotein effector of lipid glycosidase. FEBS Lett 53:243–247

    Article  PubMed  CAS  Google Scholar 

  • Ho MW, Rigby M (1975) Glucocerebrosidase. Stoichiometry of association between effector and catalytic proteins. Biochim Biophys Acta 397:267–273

    PubMed  CAS  Google Scholar 

  • Holtschmidt H, Sandhoff K, Kwon HY, Harzer K, Nakano T, Suzuki K (1991) Sulfatide activator protein: alternative splicing generates three mRNAs and a newly found mutation responsible for a clinical disease. J Biol Chem 266:7556–7560

    PubMed  CAS  Google Scholar 

  • Hopkins CR, Gibson A, Shipman M, Miller K (1990) Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum. Nature 346:335–339

    Article  PubMed  CAS  Google Scholar 

  • Harzer K, Paton BC, Poulos A, Kustermann-Kuhn B, Roggendorf W, Grisar T, Popp M (1989) Sphingolipid activator protein (SAP) deficiency in a 16-week-old atypical Gaucher disease patient and his fetal sibling: biochemical signs of combined sphingolipidoses. Eur J Pediatr 149:31–39

    Article  PubMed  CAS  Google Scholar 

  • Iber H, Kaufmann R, Pohlentz G, Schwarzmann G, Sandhoff K (1989) Identity of GA1-, GM la- and GDlb synthase in Golgi vesicles from rat liver. FEBS Lett 248:18–22

    Article  PubMed  CAS  Google Scholar 

  • Iber H, Sandhoff K (1989) Identity of GDlc, GTla and GQlb synthase in Golgi vesicles from rat liver. FEBS Lett 254:124–128

    Article  PubMed  CAS  Google Scholar 

  • Iber H, van Echten G, Klein RA, Sandhoff K (1990) pH-Dependent changes of ganglioside biosynthesis in neuronal cell culture. Eur J Cell Biol 52:236–240

    PubMed  CAS  Google Scholar 

  • Iber H, van Echten G, Sandhoff K (1991) Substrate specificity of α 2 → 3 sialytransferases in ganglioside biosynthesis of rat liver Golgi. Eur J Biochem 195:115–120

    Article  PubMed  CAS  Google Scholar 

  • Iber H, Zacharias C, Sandhoff K (1992a) The c-series gangliosides GT3, GT2 and GPlc are formed in rat liver Golgi by the same set of glycosyltransferases that catalyze the biosynthesis of asialo, a-, and b-series gangliosides. Glycobiology 2:137–142

    Article  PubMed  CAS  Google Scholar 

  • Iber H, van Echten G, Sandhoff K (1992b) Fractionation of primary cultured neurons: distribution of sialyltransferases involved in ganglioside biosynthesis. J Neurochem 58:1533–1537

    Article  PubMed  CAS  Google Scholar 

  • Kok JW, Babia T, Hoekstra D (1991) Sorting of sphingolipids in the endocytic pathway of HT 29 cells. J Cell Biol 114:231–239

    Article  PubMed  CAS  Google Scholar 

  • Koval M, Pagano RE (1989) Lipid recycling between the plasma membrane and intracellular compartments: transport and metabolism of fluorescent sphingomyelin analogs in cultured fibroblasts. J Cell Biol 108:2169–2181

    Article  PubMed  CAS  Google Scholar 

  • Koval M, Pagano RE (1990) Sorting of an internalized plasma membrane lipid between recycling and degradative pathways in normal and Niemann-Pick, type A fibroblasts. J Cell Biol 111:429–442

    Article  PubMed  CAS  Google Scholar 

  • Kretz KA, Carson GS, Morimoto S, Kishimoto Y, Fluharty AL, O’Brien JS (1990) Characterization of a mutation in a family with saposin B deficiency: a glucosylation site defect. Proc Natl Acad Sci USA 87:2541–2544

    Article  PubMed  CAS  Google Scholar 

  • Ledeen RW, Yu RK (1982) New strategies for detection and resolution of minor gangliosides as applied to brain fucogangliosides. Methods Enzymol 83:139–189

    Article  PubMed  CAS  Google Scholar 

  • Li S-C, Sonnino S, Tettamanti G, Li Y-T (1988) Characterization of a nonspecific activator protein for the enzymatic hydrolysis of glycolipids. J Biol Chem 263:6588–6591

    PubMed  CAS  Google Scholar 

  • Mandon EC, van Echten G, Birk R, Schmidt RR, Sandhoff K (1991) Sphingolipid biosynthesis in cultured neurons. Downregulation of serine palmitoyltransferase by sphingoid bases. Eur J Biochem 198:667–674

    Article  PubMed  CAS  Google Scholar 

  • Mandon E, Ehses I, Rother J, van Echten G, Sandhoff K (1992) Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase and sphinganine N-acyltransferase in mouse liver. J Biol Chem 267:11144–11148

    PubMed  CAS  Google Scholar 

  • McKanna JA, Haigier HT, Cohen S (1979) Hormone receptor topology and dynamics: morphological analysis using ferritin-labeled epidermal growth factor. Proc Natl Acad Sci USA 76:5689–5693

    Article  PubMed  CAS  Google Scholar 

  • Mehl E, Jatzkewitz H (1964) Eine Cerebrosidsulfatase aus Schweineniere. Hoppe-Seyler’s Z Physiol Chem 339:260–276

    Article  PubMed  CAS  Google Scholar 

  • Meier EM, Schwarzmann G, Fürst W, Sandhoff K (1991) The human GM2 activator protein: a substrate-specific cofactor of hexosaminidase A. J Biol Chem 266:1879–1887

    PubMed  CAS  Google Scholar 

  • Merrill AH, Wang E (1986) Biosynthesis of long-chain (sphingoid) bases from serine by LM cells. J Biol Chem 261:3764–3769

    PubMed  CAS  Google Scholar 

  • Morré DJ, Kartenbeck J, Franke WW (1979) Membrane flow and interconversions among en- domembranes. Biochim Biophys Acta 559:71–152

    PubMed  Google Scholar 

  • Moser W, Moser AB, Chen WW, Schram AW (1989) Ceramidase deficiency: Farber lipogra- nulomatosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic bases of inherited disease, 6th ed., vol. II. Mc Graw-Hill, New York, pp 1645–1654

    Google Scholar 

  • Nagai Y, Nakaishi H, Sanai Y (1986) Gene transfer as a novel approach to the gene-controlled mechanism of the cellular expression of glycosphingolipids. Chem Phys Lipids 42:91–103

    Article  PubMed  CAS  Google Scholar 

  • Nakakuma H, Sanai Y, Shiroki K, Nagai Y (1984) Gene-regulated expression of glycolipids: appearance of GD3 ganglioside in rat cells on transfection with transforming gene E 1 of human adenovirus type 12 DNA and its transcriptional subunits. J Biochem 96:1471–1480

    CAS  Google Scholar 

  • Nakano T, Sandhoff K, Stümper J, Chrisomanou H, Suzuki K (1989) Structure of full-length cDNA coding for sulfatide activator, a co-β-glucosidase and two other homologous proteins: two alternate forms of the sulfatide activator. J Biochem (Tokyo) 105:152–154

    CAS  Google Scholar 

  • Ong DE, Brady RN (1973) In vivo studies on the introduction of the 4-t-double bond of the sphingenene moiety of rat brain ceramides. J Biol Chem 248:3884–3888

    PubMed  CAS  Google Scholar 

  • Pohlentz G, Klein D, Schwarzmann G, Schmitz D, Sandhoff K (1988) Both GA2-, GM2, and GD2 synthases and GM lb, GDI a and GTlb synthases are single enzymes in Golgi vesicles from rat liver. Proc Natl Sci USA 85:7044–7048

    Article  CAS  Google Scholar 

  • Rafi MA, Zhang X-L, De Gala G, Wenger DA (1990) Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy. Biochem Biophys Res Commun 166:1017–1023

    Article  PubMed  CAS  Google Scholar 

  • Renfrew CA, Hubbard AL (1991) Degradation of epidermal growth factor receptor in rat liver. Membrane topology through the lysosomal pathway. J Biol Chem 266:21265–21273

    PubMed  CAS  Google Scholar 

  • Rother J, van Echten G, Schwarzmann G, Sandhoff K (1992) Biosynthesis of sphingolipids: di- hydroceramide and not sphinganine is desaturated by cultured cells. Biochem Biophys Res Commun 189:14–20

    Article  PubMed  CAS  Google Scholar 

  • Sandhoff K, Christomanou H (1979) Biochemistry and genetics of gangliosidoses. Hum Genet 50:107–143

    Article  PubMed  CAS  Google Scholar 

  • Sandhoff K, Conzelmann E, Neufeld ET, Kaback MM, Suzuki K (1989) The GM2-gangliosi- dosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic bases of inherited disease, 6th ed., vol. II. Mc Graw-Hill, New York, pp 1807–1839

    Google Scholar 

  • Sandhoff K, van Echten G, Schröder M, Schnabel D, Suzuki K (1992) Metabolism of glycolipids. The role of glycolipid-binding proteins in the function and pathobiochemistry of lyso- somes. Biochem Soc Trans 20:695–699

    PubMed  CAS  Google Scholar 

  • Schnabel D, Schröder M, Sandhoff K (1991) Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease. FEBS Lett 284:57–59

    Article  PubMed  CAS  Google Scholar 

  • Schnabel D, Schröder M, Fürst W, Klein A, Hurwitz R, Zenk T, Weber G, Harzer K, Paton B, Poulos A, Suzuki K, Sandhoff K (1992) Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. J Biol Chem 267:3312–3315

    PubMed  CAS  Google Scholar 

  • Schwarzmann G, Sandhoff K (1990) Metabolism and intracellular transport of glycosphingoli- pids. Perspectives in biochemistry, Biochemistry 29:10865–10871

    Article  PubMed  CAS  Google Scholar 

  • Stoffel W, Le Kim D, Sticht G (1968) Metabolism of sphingosine bases: biosynthesis of dihy- drosphingosine in vitro. Hoppe-Seyler’s Z Physiol Chem 349:664–670

    Article  PubMed  CAS  Google Scholar 

  • Stoffel W, Bister K (1974) Desaturation of sphinganine. Ceramide and sphingomyelin metabolism in the rat and in BHK 21 cells in tissue culture. Hoppe-Seyler’s Z Physiol Chem 355:911–923

    Article  PubMed  CAS  Google Scholar 

  • Svennerholm L (1984) Biological significance of gangliosides. In: Dreyfus H, Massarelli R, Freysz L, Rebel G (eds) Cellular and pathological aspects of glycoconjugate metabolism, vol 126. INSERM, France, pp 21–44

    Google Scholar 

  • Thompson LK, Horowitz PM, Bently KL, Thomas DD, Alderete JF, Klebe RJ (1986) Localization of the ganglioside-binding site of fibronectin. J Biol Chem 261:5209–5214

    PubMed  CAS  Google Scholar 

  • Tiemeyer M, Yasuda Y, Schnaar RL (1989) Ganglioside-specific binding protein on rat brain membranes. J Biol Chem 264:1671–1681

    PubMed  CAS  Google Scholar 

  • Trinchera M, Fabbri M, Ghidoni R (1991) Topography of gly cosy transferases involved in the initial glycosylations of gangliosides. J Biol Chem 266:20907–20912

    PubMed  CAS  Google Scholar 

  • van Echten G, Sandhoff K (1989) Modulation of ganglioside biosynthesis in primary cultured neurons. J Neurochem 52:207–214

    Article  PubMed  Google Scholar 

  • van Echten G, Iber H, Stotz H, Takatsuki A, Sandhoff K (1990a) Uncoupling of ganglioside biosynthesis by Brefeldin A. Eur J Cell Biol 51:135–139

    PubMed  Google Scholar 

  • van Echten G, Birk R, Brenner-Weiss G, Schmidt RR, Sandhoff K (1990b) Modulation of sphingolipid biosynthesis in primary cultured neurons by long-chain bases. J Biol Chem 265:9333–9339

    PubMed  Google Scholar 

  • Vogel A, Schwarzmann G, Sandhoff K (1991) Glycosphingolipid specificity of the human sul- fatide activator protein. Eur J Biochem 200:591–597

    Article  PubMed  CAS  Google Scholar 

  • Wessling-Resnick M, Braell WA (1990) The sorting and segregation mechanism of the en- docytic pathway is functional in a cell-free system. J Biol Chem 265:690–699

    PubMed  CAS  Google Scholar 

  • Yusuf HKM, Schwarzmann G, Pohlentz G, Sandhoff K (1987) Oligosialogangliosides inhibit GM2- and GD3-synthesis in isolated Golgi vesicles from rat liver. Hoppe Seyler’s Z Physiol Chem 368:455–462

    Article  CAS  Google Scholar 

  • Zhang X-L, Rafi MA, De Gala G, Wenger DA (1990) Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. Proc Natl Acad Sci USA 87:1426–1430

    Article  PubMed  CAS  Google Scholar 

  • Zhang X-L, Rafi MA, De Gala G, Wenger DA (1991) The mechanism for a 33-nucleotide insertion in messenger RNA causing sphingolipid activator protein (SAP-1) — deficient metachromatic leukodystrophy. Hum Genet 87:211–215

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Straße 1, D-53121, Bonn 1, Germany

    K. Sandhoff & G. van Echten

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  1. K. Sandhoff
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  2. G. van Echten
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Editors and Affiliations

  1. Institut für Biochemie I der Universität, Universität Heidelberg, Im Neuenheimer Feld 328, D-69120, Heidelberg, Germany

    Felix Wieland

  2. Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, D-14195, Berlin, Germany

    Werner Reutter

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© 1994 Springer-Verlag Berlin Heidelberg

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Sandhoff, K., van Echten, G. (1994). Topology and Regulation of Ganglioside Metabolism — Function and Pathobiochemistry of Sphingolipid Activator Proteins. In: Wieland, F., Reutter, W. (eds) Glyco-and Cellbiology. Colloquium der Gesellschaft für Biologische Chemie 22.–24. April 1993 in Mosbach/Baden, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78729-4_8

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  • DOI: https://doi.org/10.1007/978-3-642-78729-4_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78731-7

  • Online ISBN: 978-3-642-78729-4

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