Undersulfation of proteoglycans synthesized by chondrocytes from a patient with achondrogenesis type 1B homozygous for an L483P substitution in the diastrophic dysplasia sulfate transporter.

Détails

ID Serval
serval:BIB_DCFD45F9AACE
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Undersulfation of proteoglycans synthesized by chondrocytes from a patient with achondrogenesis type 1B homozygous for an L483P substitution in the diastrophic dysplasia sulfate transporter.
Périodique
Journal of Biological Chemistry
Auteur(s)
Rossi A., Bonaventure J., Delezoide A.L., Cetta G., Superti-Furga A.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
1996
Volume
271
Numéro
31
Pages
18456-18464
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Achondrogenesis type 1B is an autosomal recessive, lethal chondrodysplasia caused by mutations in the gene encoding a sulfate/chloride antiporter of the cell membrane (Superti-Furga, A., Hästbacka, J., Wilcox, W. R., Cohn, D. H., van der Harten, J. J., Rossi, A., Blau, N., Rimoin, D. L., Steinmann, B., Lander, E. S., and Gitzelmann, R.(1996) Nat. Genet. 12, 100-102). To ascertain the consequences of the sulfate transport defect on proteoglycan synthesis, we studied the structure and sulfation of proteoglycans in cartilage tissue and in fibroblast and chondrocyte cultures from a fetus with achondrogenesis 1B. Proteoglycans extracted from epiphyseal cartilage and separated on agarose gels migrated more slowly than controls and stained poorly with alcian blue. The patient's cultured cells showed reduced incorporation of [35S]sulfate relative to [3H]glucosamine, impaired uptake of sulfate, and higher resistance to chromate toxicity compared to control cells. Epiphyseal chondrocytes cultured in alginate beads synthesized proteoglycans of normal molecular size as judged by gel filtration chromatography, but undersulfated as judged by ion exchange chromatography and by the amount of nonsulfated disaccharide. High performance liquid chromatography analysis of chondroitinase-digested proteoglycans showed that sulfated disaccharides were present, although in reduced amounts, indicating that at least in vitro, other sources of sulfate can partially compensate for sulfate deficiency. A t1475c transition causing a L483P substitution in the eleventh transmembrane domain of the sulfate/chloride antiporter was present on both alleles in the patient who was the product of a consanguineous marriage. The results indicate that the defect of sulfate transport is expressed in both chondrocytes and fibroblasts and results in the synthesis of proteoglycans bearing glycosaminoglycan chains which are poorly sulfated but of normal length.
Mots-clé
Achondroplasia/genetics, Achondroplasia/metabolism, Amino Acid Sequence, Anion Transport Proteins, Base Sequence, Biological Transport, Active, Carrier Proteins/genetics, Cartilage/metabolism, Cartilage/pathology, Cells, Cultured, Consanguinity, DNA/genetics, Female, Fetal Diseases/genetics, Fetal Diseases/metabolism, Fibroblasts/metabolism, Homozygote, Humans, Membrane Transport Proteins, Molecular Sequence Data, Molecular Structure, Point Mutation, Pregnancy, Proteoglycans/biosynthesis, Proteoglycans/chemistry, Sulfates/chemistry, Sulfates/metabolism
Pubmed
Web of science
Création de la notice
14/03/2011 16:14
Dernière modification de la notice
20/08/2019 16:01
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