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. 1990 Feb;87(4):1342–1346. doi: 10.1073/pnas.87.4.1342

A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome.

E Quentin 1, A Gladen 1, L Rodén 1, H Kresse 1
PMCID: PMC53471  PMID: 2106134

Abstract

A small proteoglycan that contains only a single dermatan sulfate chain is the main proteoglycan synthesized by skin fibroblasts. Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. This abnormality is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-beta-galactosyltransferase; EC 2.4.1.133), which catalyzes the second glycosyl transfer reaction in the assembly of the dermatan sulfate chain. The glycosaminoglycan-free core protein secreted by the patient's fibroblasts bears an unsubstituted xylose residue. The mutant enzyme is abnormally thermolabile. Preincubation of fibroblasts at 41 degrees C leads to a further reduction in the production of mature proteoglycan and affects the capacity for glycosaminoglycan synthesis on p-nitrophenyl beta-D-xyloside more strongly in the mutant than in control cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chopra R. K., Pearson C. H., Pringle G. A., Fackre D. S., Scott P. G. Dermatan sulphate is located on serine-4 of bovine skin proteodermatan sulphate. Demonstration that most molecules possess only one glycosaminoglycan chain and comparison of amino acid sequences around glycosylation sites in different proteoglycans. Biochem J. 1985 Nov 15;232(1):277–279. doi: 10.1042/bj2320277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Esko J. D., Stewart T. E., Taylor W. H. Animal cell mutants defective in glycosaminoglycan biosynthesis. Proc Natl Acad Sci U S A. 1985 May;82(10):3197–3201. doi: 10.1073/pnas.82.10.3197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Esko J. D., Weinke J. L., Taylor W. H., Ekborg G., Rodén L., Anantharamaiah G., Gawish A. Inhibition of chondroitin and heparan sulfate biosynthesis in Chinese hamster ovary cell mutants defective in galactosyltransferase I. J Biol Chem. 1987 Sep 5;262(25):12189–12195. [PubMed] [Google Scholar]
  4. Glössl J., Beck M., Kresse H. Biosynthesis of proteodermatan sulfate in cultured human fibroblasts. J Biol Chem. 1984 Nov 25;259(22):14144–14150. [PubMed] [Google Scholar]
  5. Heinegård D., Björne-Persson A., Cöster L., Franzén A., Gardell S., Malmström A., Paulsson M., Sandfalk R., Vogel K. The core proteins of large and small interstitial proteoglycans from various connective tissues form distinct subgroups. Biochem J. 1985 Aug 15;230(1):181–194. doi: 10.1042/bj2300181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kresse H., Rosthøj S., Quentin E., Hollmann J., Glössl J., Okada S., Tønnesen T. Glycosaminoglycan-free small proteoglycan core protein is secreted by fibroblasts from a patient with a syndrome resembling progeroid. Am J Hum Genet. 1987 Sep;41(3):436–453. [PMC free article] [PubMed] [Google Scholar]
  7. Krusius T., Ruoslahti E. Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7683–7687. doi: 10.1073/pnas.83.20.7683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  10. Mourão P. A., Kato S., Donnelly P. V. Spondyloepiphyseal dysplasia, chondroitin sulfate type: a possible defect of PAPS--chondroitin sulfate sulfotransferase in humans. Biochem Biophys Res Commun. 1981 Jan 30;98(2):388–396. doi: 10.1016/0006-291x(81)90852-4. [DOI] [PubMed] [Google Scholar]
  11. Nakazawa K., Hassell J. R., Hascall V. C., Lohmander L. S., Newsome D. A., Krachmer J. Defective processing of keratan sulfate in macular corneal dystrophy. J Biol Chem. 1984 Nov 25;259(22):13751–13757. [PubMed] [Google Scholar]
  12. Nelles L. P., Bamburg J. R. Rapid visualization of protein--dodecyl sulfate complexes in polyacrylamide gels. Anal Biochem. 1976 Jun;73(2):522–531. doi: 10.1016/0003-2697(76)90202-5. [DOI] [PubMed] [Google Scholar]
  13. O'Donnell C. M., Kaczman-Daniel K., Goetinck P. F., Vertel B. M. Nanomelic chondrocytes synthesize a glycoprotein related to chondroitin sulfate proteoglycan core protein. J Biol Chem. 1988 Nov 25;263(33):17749–17754. [PubMed] [Google Scholar]
  14. Rauch U., Glössl J., Kresse H. Comparison of small proteoglycans from skin fibroblasts and vascular smooth-muscle cells. Biochem J. 1986 Sep 1;238(2):465–474. doi: 10.1042/bj2380465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rosenberg L. C., Choi H. U., Tang L. H., Johnson T. L., Pal S., Webber C., Reiner A., Poole A. R. Isolation of dermatan sulfate proteoglycans from mature bovine articular cartilages. J Biol Chem. 1985 May 25;260(10):6304–6313. [PubMed] [Google Scholar]
  16. Saito H., Yamagata T., Suzuki S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J Biol Chem. 1968 Apr 10;243(7):1536–1542. [PubMed] [Google Scholar]
  17. Schwartz N. B. Biosynthesis of chondroitin sulfate. Role of phospholipids in the activity of UDP-D-galactose: D-xylose galactosyltransferase. J Biol Chem. 1976 Jan 25;251(2):285–291. [PubMed] [Google Scholar]
  18. Schwartz N. B., Rodén L. Biosynthesis of chondroitin sulfate. Solubilization of chondroitin sulfate glycosyltransferases and partial purification of uridine diphosphate-D-galactose:D-xylose galactosyltrans. J Biol Chem. 1975 Jul 10;250(13):5200–5207. [PubMed] [Google Scholar]
  19. Schwartz N. B., Rodén L., Dorfman A. Biosynthesis of chondroitin sulfate: interaction between xylosyltransferase and galactosyltransferase. Biochem Biophys Res Commun. 1974 Feb 4;56(3):717–724. doi: 10.1016/0006-291x(74)90664-0. [DOI] [PubMed] [Google Scholar]
  20. Sugahara K., Schwartz N. B. Defect in 3'-phosphoadenosine 5'-phosphosulfate synthesis in brachymorphic mice. II. Tissue distribution of the defect. Arch Biochem Biophys. 1982 Apr 1;214(2):602–609. doi: 10.1016/0003-9861(82)90065-0. [DOI] [PubMed] [Google Scholar]
  21. Yamaguchi Y., Ruoslahti E. Expression of human proteoglycan in Chinese hamster ovary cells inhibits cell proliferation. Nature. 1988 Nov 17;336(6196):244–246. doi: 10.1038/336244a0. [DOI] [PubMed] [Google Scholar]

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