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Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis

Nature Genetics volume 15, pages 316–320 (1997)Cite this article

Abstract

Sialidase (neuraminidase, EC 3.2.1.18) catalyses the hydrolysis of terminal sialic acid residues of glyconjugates. Sialidase has been well studied in viruses and bacteria where it destroys the sialic acid-containing receptors at the surface of host cells1–3, and mobilizes bacterial nutrients4. In mammals, three types of sialidases, lysosomal, plasma membrane and cytosolic, have been described5,7. For lysosomal sialidase in humans, the primary genetic deficiency results in an autosomal recessive disease, sialidosis, associated with tissue accumulation and urinary excretion of sialylated oligosaccharides and glycolipids. Sialidosis includes two main clinical variants: late-onset, sialidosis type I, characterized by bilateral macular cherry-red spots and myoclonus8,9, and infantile-onset, sialidosis type II, characterized by skeletal dysplasia, mental retardation and hepatosplenomegaly10–12. We report the identification of human lysosomal sialidase cDNA, its cloning, sequencing and expression. Examination of six sialidosis patients revealed three mutations, one frameshift insertion and two missense. We mapped the lysosomal sialidase gene to human chromosome 6 (6p21.3), which is consistent with the previous chromosomal assignment of this gene in proximity to the HLA locus.

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References

  1. Hirst, G.K. The agglutination of red cells by allantoic fluid of chick embryos infected with influenza virus. Science 94, 22–23 (1941).

    Article  CAS  Google Scholar 

  2. Gottschalk, A. & Lind, P.E. Product of interaction between influenza virus enzyme arid ovomucin. Nature 164, 232–233 (1949).

    Article  CAS  Google Scholar 

  3. Galen, J.E. et al. Role of Vibrio cholerae neuraminidase in the function of cholera toxin. Infect. immun. 60, 406–415 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Corfield, T. Bacterial sialidases—roles in pathogenicity and nutrition. Glycobiology 2, 509–521 (1992).

    Article  CAS  Google Scholar 

  5. Verheijen, F.W. et al. Two genetically different mu-nana neuraminidases in human leucocytes. Biochem. Biophys. Res. Commun. 117, 470–478 (1983).

    Article  CAS  Google Scholar 

  6. Miyagi, T. Sagawa, J. Konno, K. & Tsuiki, S. Immunological discrimination of intralysosomal, cytosolic, and two membrane sialidases present in rat tissues. J. Biochem. 107, 794–798 (1990).

    Article  CAS  Google Scholar 

  7. Schneider-Jakob, H.R. & Cantz, M. Lysosomal and plasma membrane ganglioside GM3 sialidases of cultured human fibroblasts. Differentiation by detergents and inhibitors. Biol. Chem. Hoppe-Seyler 372, 443–450 (1991).

    Article  CAS  Google Scholar 

  8. Durand, P. et al. Sialidosis (mucolipidosis I). Helv. Paedia. Acta 32, 391–400 (1977).

    CAS  Google Scholar 

  9. O'Brien, J.S. The cherry-red spot-myoclonus syndrome: a newly recognized inherited lysosomal storage disease due to acid neuraminidase deficiency. Clin. Genet. 14, 55–60 (1979).

    Article  Google Scholar 

  10. Till, J.S. Roach, E.S. & Burton, B.K. Sialidosis (neuraminidase deficiency) types I and II: neuro-opthalmic manifestations. J. Clin. Neur-Ophtalmol. 7, 40–44 (1987).

    CAS  Google Scholar 

  11. Oohira, T. Nagata, N. Akaboshi, I. Matsuda, I. & Naito, S. The infantifle form of Sialidosis type II associated with congenital adrenal hyperplasia: possible linkage between HLA and the neuraminidase deficiency gene. Hum. Genet 70, 341–343 (1985).

    Article  CAS  Google Scholar 

  12. Beck, M. et al. Neuraminidase deficiency presenting as non-immune hydrops fetalis. Eur. J. Pediatr. 143.135–139 (1984).

    Article  CAS  Google Scholar 

  13. Roggentin, P. et al. Conserved sequences in bacterial and viral sialidases. Glycocon. J. 6, 349–353 (1989).

    Article  CAS  Google Scholar 

  14. Rothe, B. Rothe, B. Roggentin, P. & Schauer, R. The sialidase gene from Clostridium septicum: cloning, sequencing, expression in Escherichia coli and identification of conserved sequences in sialidases and other proteins. Mol. Gen. Genet. 226, 190–197 (1991).

    Article  CAS  Google Scholar 

  15. Crennell, S.J. Carman, E.F. Laver, W.G. Vimr, E.R. & Taylor, G.L. Crystal structure of a bacterial sialidase (from Salmonella typhimurium LT2) shows the same fold as an influenza virus neuraminidase. Proc. Natl. Acad. Sci. USA 90, 9852–9856 1993).

    Article  CAS  Google Scholar 

  16. Miyagi, T. et al. Molecular cloning and expression of cDNA encoding rat skeletal muscle cytosolic sialidase. J. Biol. Chem. 268, 26435–26440 (1993).

    CAS  PubMed  Google Scholar 

  17. Ferrari, J. Harris, R. & Warner, T.G. Cloning and expression of a soluble sialidase from Chinese hamster ovary cells: sequence alignment similarities to bacterial sialidases. Glycobiology 4, 367–373 (1994).

    Article  CAS  Google Scholar 

  18. Aerts, J.M. et al. Glucocerebrosidase, a lysosomal enzyme that does not undergo oligosaccharide phosphorylation. Biochim. Biophys. Acta 964, 303–308 (1988).

    Article  CAS  Google Scholar 

  19. Guarnieri, F.G. Arterburn, L.M. Penno, M.B. Cha, Y. & August, J.T. The motif Tyr-X-X-hydrophobic residue mediates lysosomal membrane targeting of lysosome-associated membrane protein. J. Biol. Chem. 268, 1941–1946 (1993).

    CAS  PubMed  Google Scholar 

  20. Sosa, M.A. Schmidt, B. von Figura, K. & Hille-Rehfeld, A. In vitro binding of plasma membrane-coated vesicle adaptors to the cytoplasmic domain of lysosomal acid phosphatase. J. Biol. Chem. 268, 12537–12543 (1993).

    CAS  PubMed  Google Scholar 

  21. Lehmann, L.E. . et al. The internalization signal in the cytoplasmic tail of lysosomal acid phosphatase consists of the hexapeptide PGYRHV. EMBO J. 11, 4391–4399 (1992).

    Article  CAS  Google Scholar 

  22. Waheed, A. et al. Human lysosomal acid phosphatase is transported as a transmembrane protein to lysosomes in transfected baby hamster kidney cells. EMBO J. 7, 2351–2358 (1988).

    Article  CAS  Google Scholar 

  23. Gottschalk, S. Waheed, A. Schmidt, B. Laidler, P. & von Figura,K. Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol proteinase and a lysosomal aspartyl proteinase. EMBO J. 8, 3125–3219 (1989).

    Article  Google Scholar 

  24. D'Agrosa, R.M. & Callahan, J.W. In vitro activation of neuraminidase in the beta-galactosidase-neuraminidase-protective protein complex by cathepsin C. Biochem. Biophys. Res. Commun. 157, 770–775 (1988).

    Article  CAS  Google Scholar 

  25. Hiraiwa, M. et al. Activation of human lysosomal sialidase. J. Biochem. 114, 901–905 (1993).

    Article  CAS  Google Scholar 

  26. Neote, K. Brown, C.A. Mahuran, D.J. & Gravel, R.A. Translation initiation in the HEXB gene encoding the β-subunit of human β-hexosaminidase. J. Biol. Chem. 265, 20799–20806 (1990).

    CAS  PubMed  Google Scholar 

  27. Jones, D.T. Taylor, W.R. & Thornton, J.M. A new approch to protein fold recognition. Nature 358, 86–89 (1992).

    Article  CAS  Google Scholar 

  28. Roggentin, P. Schauer, R. Hoyer, L.L. & Vimr, E.R. The sialidase superfamily and its spread by horizontal gene transfer. Mol. Microbiol. 9, 915–921 (1993).

    Article  CAS  Google Scholar 

  29. Triggs-Raine, B.L. Akerman, B.R. Clarke, J.T. & Gravel, R.A. Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease. Am. J. Hum. Genet 49, 1041–1054 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. MacGregor, G.R. & Caskey, C.T. Construction of plasmids that express E. coli β-galactosidase in mammalian cells. Nucl. Acids Res. 17, 2365 (1989).

    Article  CAS  Google Scholar 

  31. Womack, J.E. Yan, D.L. & Potier, M. Gene for neuraminidase activity on mouse chromosome 17 near h-2: pleiotropic effects on multiple hydrolases. Science 212, 63–65 (1981).

    Article  CAS  Google Scholar 

  32. Samollow, P.F. Ford, A.L. Kunz, H.W. & Gill, T.J. Mapping the Neu-1 locus to the major histocompatibility complex (RT1) in the rat. Immunogenet. 26, 188–189 (1987).

    Article  CAS  Google Scholar 

  33. Maniatis, T. Fritsch, E.F. & Sambrook, J. (eds) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982).

    Google Scholar 

  34. Cowan, N.J. Dobner, P.R. Fuchs, E.V. & Cleveland, D.W. Expression of human alpha-tubulin genes: interspecies conservation of 3′ untranslated regions. Mol. Cell. Biol. 3, 1738–1745 (1983).

    Article  CAS  Google Scholar 

  35. Lennon, G.G. Auffray, C. Polymeropoulos, M. & Soares, M.B. The I.M.A.G.E. consortium: An integrated molecular analysis of genomes and their expression. Genomics 33, 151–152 (1996).

    Article  CAS  Google Scholar 

  36. Rome, L.H. Garvin, A.J. Allietta, M.M. & Neufeld, E.F. Two species of lysosomal organelles in cultured human fibroblasts. Cell 17, 143–153 (1979).

    Article  CAS  Google Scholar 

  37. Potier, M. Mameli, L. Belisle, M. Dallaire, L. & Melançon, S.B. Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferylα-D-N-acetylneuraminate) substrate. Anal. Biochem. 94, 287–296 (1979).

    Article  CAS  Google Scholar 

  38. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976).

    Article  CAS  Google Scholar 

  39. Lichter, P. & Cremer, T. Chromosome analysis by nonisotopic in situ hybridization. In Human cytogenetics. A practical approach Vol. 1 (Eds. Rooney, D.E. & Czepulkowski, B.H.) 157–192 (Oxford University Press, New York, 1992).

    Google Scholar 

  40. Lemieux, N. Dutrillaux, B. & Viegas-Péquignot, E. A simple method for simultaneous R- or G-banding and fluorescence in situ hybridization of small single-copy genes. Cytogenet. Cell. Genet. 59, 311–312 (1992).

    Article  CAS  Google Scholar 

  41. Varghese, J.N. Webster, R.G. Laver, W.G. & Colman, P.M. Structure of an escape mutant of glycoprotein N2 neuraminidase of influenza virus A/Tokyo/3/67 at 3A. J. Mol. Biol. 200, 201–203 (1988).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Service de Génétique Médicale, Département de Pédiatrie, Hôpital Sainte-Justine, 3175 Chemin Sainte-Catherine, Université de Montréal, Montréal, Québec, H3T 1C5, Canada

    Alexey V. Pshezhetsky, Catherine Richard, Lorraine Michaud, Shupei Wang, Marc-André Elsliger, Jingyi Qu, Louis Dallaire & Michel Potier

  2. Montréal Children's Hospital Research Institute, Department of Pediatrics and Human Genetics, McGill University, Montréal, Québec, Canada

    Suleiman Igdoura, Daniel Leclerc & Roy Gravel

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Pshezhetsky, A., Richard, C., Michaud, L. et al. Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis. Nat Genet 15, 316–320 (1997). https://doi.org/10.1038/ng0397-316

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