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. 1987 Dec 15;248(3):697–701. doi: 10.1042/bj2480697

Altered molecular size of N-acetylglucosamine 1-phosphotransferase in I-cell disease and pseudo-Hurler polydystrophy.

Y Ben-Yoseph 1, M Potier 1, D A Mitchell 1, B A Pack 1, S B Melançon 1, H L Nadler 1
PMCID: PMC1148605  PMID: 2829837

Abstract

The size of the mutant N-acetylglucosamine 1-phosphotransferase in Golgi membranes from fibroblasts of patients with I-cell disease and classical pseudo-Hurler polydystrophy, which comprised one complementation group characterized by deficiency towards both artificial and natural acceptor substrates, was significantly smaller than the normal enzyme, 151-174 kDa compared with 225-278 kDa. The size of the mutant enzyme from cell lines of patients with variant forms of pseudo-Hurler polydystrophy, which comprised another complementation group characterized by normal activity towards mono- and oligo-saccharide substrates, was significantly larger than the normal enzyme, ranging from 321 to 356 kDa in two families and from 528 to 547 kDa in a third family. These findings suggest that the mutations in I-cell disease and classical pseudo-Hurler polydystrophy result in a missing enzyme component, which renders the enzyme catalytically inefficient toward any type of acceptor substrate. In contrast, the mutations in the variant forms of pseudo-Hurler polydystrophy produce a larger enzyme molecule which is active toward small substrates but is incapable of binding natural lysosomal glycoprotein substrates.

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Selected References

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  1. Beauregard G., Giroux S., Potier M. Target size analysis by radiation inactivation: a large capacity tube rack for irradiation in a Gammacell 220. Anal Biochem. 1983 Jul 15;132(2):362–364. doi: 10.1016/0003-2697(83)90021-0. [DOI] [PubMed] [Google Scholar]
  2. Beauregard G., Potier M. Radiation inactivation of enzymes at low dose rates: identical molecular weights of rat liver cytosolic and lysosomal neuraminidases. Anal Biochem. 1982 May 15;122(2):379–384. doi: 10.1016/0003-2697(82)90299-8. [DOI] [PubMed] [Google Scholar]
  3. Beauregard G., Potier M. Temperature dependence of the radiation inactivation of proteins. Anal Biochem. 1985 Oct;150(1):117–120. doi: 10.1016/0003-2697(85)90448-8. [DOI] [PubMed] [Google Scholar]
  4. Ben-Yoseph Y., Baylerian M. S., Momoi T., Nadler H. L. Thermal activation of hexosaminidase A in a genetic compound with Tay-Sachs disease. J Inherit Metab Dis. 1983;6(3):95–100. doi: 10.1007/BF01800733. [DOI] [PubMed] [Google Scholar]
  5. Ben-Yoseph Y., Baylerian M. S., Nadler H. L. Radiometric assays of N-acetylglucosaminylphosphotransferase and alpha-N-acetylglucosaminyl phosphodiesterase with substrates labeled in the glucosamine moiety. Anal Biochem. 1984 Nov 1;142(2):297–304. doi: 10.1016/0003-2697(84)90468-8. [DOI] [PubMed] [Google Scholar]
  6. Ben-Yoseph Y., Pack B. A., Mitchell D. A., Elwell D. G., Potier M., Melançon S. B., Nadler H. L. Characterization of the mutant N-acetylglucosaminylphosphotransferase in I-cell disease and pseudo-Hurler polydystrophy: complementation analysis and kinetic studies. Enzyme. 1986;35(2):106–116. doi: 10.1159/000469330. [DOI] [PubMed] [Google Scholar]
  7. Ben-Yoseph Y., Potier M., Pack B. A., Mitchell D. A., Melançon S. B., Nadler H. L. Molecular size of N-acetylglucosaminylphosphotransferase and alpha-N-acetylglucosaminyl phosphodiesterase as determined in situ in Golgi membranes by radiation inactivation. Biochem J. 1986 May 1;235(3):883–886. doi: 10.1042/bj2350883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ben-Yoseph Y., Reid J. E., Shapiro B., Nadler H. L. Diagnosis and carrier detection of Tay-Sachs disease: direct determination of hexosaminidase A using 4-methylumbelliferyl derivatives of beta-N-acetylglucosamine-6-sulfate and beta-N-acetylgalactosamine-6-sulfate. Am J Hum Genet. 1985 Jul;37(4):733–740. [PMC free article] [PubMed] [Google Scholar]
  9. 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. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  10. Choy F. Y., Woo M., Potier M. In situ radiation-inactivation size of fibroblast membrane-bound acid beta-glucosidase in Gaucher type 1, type 2 and type 3 disease. Biochim Biophys Acta. 1986 Mar 7;870(1):76–81. doi: 10.1016/0167-4838(86)90010-5. [DOI] [PubMed] [Google Scholar]
  11. Geiger B., Ben-Yoseph Y., Arnon R. Purification of human hexosaminidases A and B by affinity chromatography. FEBS Lett. 1974 Sep 1;45(1):276–281. doi: 10.1016/0014-5793(74)80861-6. [DOI] [PubMed] [Google Scholar]
  12. Hasilik A., Waheed A., von Figura K. Enzymatic phosphorylation of lysosomal enzymes in the presence of UDP-N-acetylglucosamine. Absence of the activity in I-cell fibroblasts. Biochem Biophys Res Commun. 1981 Feb 12;98(3):761–767. doi: 10.1016/0006-291x(81)91177-3. [DOI] [PubMed] [Google Scholar]
  13. Honey N. K., Miller A. L., Shows T. B. The mucolipidoses: identification by abnormal electrophoretic patterns of lysosomal hydrolases. Am J Med Genet. 1981;9(3):239–253. doi: 10.1002/ajmg.1320090310. [DOI] [PubMed] [Google Scholar]
  14. Honey N. K., Mueller O. T., Little L. E., Miller A. L., Shows T. B. Mucolipidosis III is genetically heterogeneous. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7420–7424. doi: 10.1073/pnas.79.23.7420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lang L., Kornfeld S. A simplified procedure for synthesizing large quantities of highly purified uridine [beta-32P]diphospho-N-acetylglucosamine. Anal Biochem. 1984 Jul;140(1):264–269. doi: 10.1016/0003-2697(84)90163-5. [DOI] [PubMed] [Google Scholar]
  16. Little L. E., Mueller O. T., Honey N. K., Shows T. B., Miller A. L. Heterogeneity of N-acetylglucosamine 1-phosphotransferase within mucolipidosis III. J Biol Chem. 1986 Jan 15;261(2):733–738. [PubMed] [Google Scholar]
  17. Maret A., Potier M., Salvayre R., Douste-Blazy L. Modification of subunit interaction in membrane-bound acid beta-glucosidase from Gaucher disease. FEBS Lett. 1983 Aug 22;160(1-2):93–97. doi: 10.1016/0014-5793(83)80943-0. [DOI] [PubMed] [Google Scholar]
  18. Mueller O. T., Honey N. K., Little L. E., Miller A. L., Shows T. B. Mucolipidosis II and III. The genetic relationships between two disorders of lysosomal enzyme biosynthesis. J Clin Invest. 1983 Sep;72(3):1016–1023. doi: 10.1172/JCI111025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Okada S., Kato T., Oshima T., Yutaka T., Yabuuchi H. Heterogeneity in mucolipidosis II (I-cell disease). Clin Genet. 1983 Feb;23(2):155–159. doi: 10.1111/j.1399-0004.1983.tb01865.x. [DOI] [PubMed] [Google Scholar]
  20. Reitman M. L., Kornfeld S. Lysosomal enzyme targeting. N-Acetylglucosaminylphosphotransferase selectively phosphorylates native lysosomal enzymes. J Biol Chem. 1981 Dec 10;256(23):11977–11980. [PubMed] [Google Scholar]
  21. Reitman M. L., Varki A., Kornfeld S. Fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5'-diphosphate-N-acetylglucosamine: glycoprotein N-acetylglucosaminylphosphotransferase activity. J Clin Invest. 1981 May;67(5):1574–1579. doi: 10.1172/JCI110189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sandberg P. O., Marzella L., Glaumann H. A method for rapid isolation of rough and smooth microsomes and Golgi apparatus from rat liver in the same sucrose gradient. Exp Cell Res. 1980 Dec;130(2):393–400. doi: 10.1016/0014-4827(80)90017-8. [DOI] [PubMed] [Google Scholar]
  23. Shows T. B., Mueller O. T., Honey N. K., Wright C. E., Miller A. L. Genetic heterogeneity of I-cell disease is demonstrated by complementation of lysosomal enzyme processing mutants. Am J Med Genet. 1982 Jul;12(3):343–353. doi: 10.1002/ajmg.1320120312. [DOI] [PubMed] [Google Scholar]
  24. Varki A. P., Reitman M. L., Kornfeld S. Identification of a variant of mucolipidosis III (pseudo-Hurler polydystrophy): a catalytically active N-acetylglucosaminylphosphotransferase that fails to phosphorylate lysosomal enzymes. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7773–7777. doi: 10.1073/pnas.78.12.7773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waheed A., Hasilik A., von Figura K. UDP-N-acetylglucosamine:lysosomal enzyme precursor N-acetylglucosamine-1-phosphotransferase. Partial purification and characterization of the rat liver Golgi enzyme. J Biol Chem. 1982 Oct 25;257(20):12322–12331. [PubMed] [Google Scholar]

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