Mouse chondroitin 6-sulfotransferase: molecular cloning, characterization and chromosomal mapping

Uchimura, Kenji; Kadomatsu, Kenji; Fan, Qi; Muramatsu, Hideki; Kurosawa, Nobuyuki; Kaname, Tadashi; Yamamura, Ken Ichi; Fukuta, Masakazu; Habuchi, Osami; Muramatsu, Takashi

doi:10.1093/glycob/8.5.489

Cited by 48 publications

(28 citation statements)

References 43 publications

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“…For the chicken brain, a developmentally regulated expression of this enzyme and the reaction products was reported (4). In the mouse, C6ST-1 was found in spleen and lung but also in eye, stomach, ovary, kidney, and, dependent on the developmental stage, in brain (17). Recently, the function of C6ST-1 has been further elucidated by inactivating CHST3 in the mouse (18).…”

Section: Discussionmentioning

confidence: 99%

Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement

Thiele

Sakano

Kitagawa

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

174

143

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We studied two large consanguineous families from Oman with a distinct form of spondyloepiphyseal dysplasia (SED Omani type). By using a genome-wide linkage approach, we were able to map the underlying gene to a 4.5-centimorgan interval on chromosome 10q23. We sequenced candidate genes from the region and identified a missense mutation in the chondroitin 6-O-sulfotransferase (C6ST-1) gene (CHST3) changing an arginine into a glutamine (R304Q) in the well conserved 3 -phosphoadenosine 5 -phosphosulfate binding site. C6ST-1 catalyzes the modifying step of chondroitin sulfate (CS) synthesis by transferring sulfate to the C-6 position of the N-acetylgalactosamine of chondroitin. From the crystal structures of other sulfotransferases, it could be inferred that Arg-304 is essential for the structure of the cosubstrate binding site. We used recombinant C6ST-1 to show that the identified missense mutation completely abolishes C6ST-1 activity. Disaccharide composition analysis of CS chains by anion-exchange HPLC shows that both ⌬HexA-GalNAc(6S) and ⌬HexA(2S)-GalNAc(6S) were significantly reduced in the patient's cells and that ⌬HexA-GalNAc(4S,6S), undetectable in controls, was elevated. Analysis of the patient's urine shows marked undersulfation of CS, in particular reduction in 6-O-sulfated disaccharide and an increase in the nonsulfated unit. Our results indicate that the mutation in CHST3 described here causes a specific but generalized defect of CS chain sulfation resulting in chondrodysplasia with major involvement of the spine.

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Section: Discussionmentioning

confidence: 99%

Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement

Thiele

Sakano

Kitagawa

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

174

143

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“…Homologous to Chondroitin-6-sulfotransferase-We previously cloned a cDNA encoding mouse chondroitin-6-sulfotransferase (39). By searching the expressed sequence tag data base, we found a small sequence (Genbank TM accession no.…”

Section: Molecular Cloning Of a Cdnamentioning

confidence: 99%

Molecular Cloning and Characterization of anN-Acetylglucosamine-6-O-sulfotransferase

Uchimura¹,

Muramatsu²,

Kadomatsu³

et al. 1998

Journal of Biological Chemistry

151

111

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We isolated a cDNA clone encoding mouse N-acetylglucosamine-6-O-sulfotransferase based on sequence homology to the previously cloned mouse chondroitin 6-sulfotransferase. The cDNA clone contained an open reading frame that predicts a type II transmembrane protein composed of 483 amino acid residues. The expressed enzyme transferred sulfate to the 6 position of nonreducing GlcNAc in GlcNAc␤1-3Gal␤1-4GlcNAc. Gal␤1-4GlcNAc␤1-3Gal␤1-4GlcNAc and various glycosaminoglycans did not serve as acceptors. Expression of the cDNA in COS-7 cells resulted in production of a cell-surface antigen, the epitope of which was NeuAc␣2-3Gal␤1-4(SO 4 -6)GlcNAc; double transfection with fucosyltransferase IV yielded Gal␤1-4(Fuc␣1-3)(SO 4 -6)GlcNAc antigen. The sulfotransferase mRNA was strongly expressed in the cerebrum, cerebellum, eye, pancreas, and lung of adult mice. In situ hybridization revealed that the mRNA was localized in high endothelial venules of mesenteric lymph nodes. The sulfotransferase was concluded to be involved in biosynthesis of glycoconjugates bearing the 6-sulfo N-acetyllactosamine structure such as 6-sulfo sialyl Lewis X. The products of the sulfotransferase probably include glycoconjugates with intercellular recognition signals; one candidate of such a glycoconjugate is an L-selectin ligand.

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“…The distinctive increase in 6-O-sulphated isomers of chondroitin sulphate in the injured environment (Chau and Shum, 1997) could therefore be a consequence of stimulated expression of the C6ST gene. Molecular cloning of human C6ST revealed two orthologous genes, C6ST-1 (Fukuta et al, 1995;Fukuta et al, 1998;Uchimura et al, 1998) and C6ST-2 (Kitagawa et al, 2000). Expression of both isoforms in the brain was evident during development but negligible in the adult.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

Chau

Liu

et al. 2006

Journal of Cell Science

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Cell migration is central to development and post-traumatic regeneration. The differential increase in 6-sulphated chondroitins during axonal growth in both crushed sciatic nerves and brain development suggests that chondroitin 6-sulphotransferase-1 (C6ST-1) is a key enzyme that mediates cell migration in the process. We have cloned the cDNA of the C6ST-1 gene (C6st1) (GenBank accession number AF178689) from crushed sciatic nerves of adult rats and produced ribonucleotide probes accordingly to track signs of 6-sulphated chondroitins at the site of injury. We found C6st1 mRNA expression in Schwann cells emigrating from explants of both sciatic nerve segments and embryonic dorsal root ganglia. Immunocytochemistry indicated pericellular 6-sulphated chondroitin products around C6ST-1-expressing frontier cells. Motility analysis of frontier cells in cultures subjected to staged treatment with chondroitinase ABC indicated that freshly produced 6-sulphated chondroitin moieties facilitated Schwann cell motility, unlike restrictions resulting from proteoglycan interaction with matrix components. Sciatic nerve crush provided further evidence of in vivo upregulation of the C6ST-1 gene in mobile Schwann cells that guided axonal regrowth 1-14 days post crush; downregulation then accompanied declining mobility of Schwann cells as they engaged in the myelination of re-growing axons. These findings are the first to identify upregulated C6st1 gene expression correlating with the motility of Schwann cells that guide growing axons through both developmental and injured environments.

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Mouse chondroitin 6-sulfotransferase: molecular cloning, characterization and chromosomal mapping

Cited by 48 publications

References 43 publications

Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement

Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement

Molecular Cloning and Characterization of anN-Acetylglucosamine-6-O-sulfotransferase

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

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