RRC ID 38196
著者 Ohtake-Niimi S, Kondo S, Ito T, Kakehi S, Ohta T, Habuchi H, Kimata K, Habuchi O.
タイトル Mice deficient in N-acetylgalactosamine 4-sulfate 6-o-sulfotransferase are unable to synthesize chondroitin/dermatan sulfate containing N-acetylgalactosamine 4,6-bissulfate residues and exhibit decreased protease activity in bone marrow-derived mast cells.
ジャーナル J Biol Chem
Abstract Chondroitin sulfate (CS) and dermatan sulfate (DS) containing N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6-SO(4))) show various physiological activities through interacting with numerous functional proteins. N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of N-acetylgalactosamine 4-sulfate in CS or DS to yield GalNAc(4,6-SO(4)) residues. We here report generation of transgenic mice that lack GalNAc4S-6ST. GalNAc4S-6ST-null mice were born normally and fertile. In GalNAc4S-6ST-null mice, GalNAc(4,6-SO(4)) residues in CS and DS disappeared completely, indicating that GalNAc4S-6ST should be a sole enzyme responsible for the synthesis of GalNAc(4,6-SO(4)) residues in both CS and DS. IdoA-GalNAc(4,6-SO(4)) units that account for approximately 40% of total disaccharide units of DS in the liver of the wild-type mice disappeared in the liver DS of GalNAc4S-6ST-null mice without reduction of IdoA content. Bone marrow-derived mast cells (BMMCs) derived from GalNAc4S-6ST-null mice contained CS without GlcA-GalNAc(4,6-SO(4)) units. Tryptase and carboxypeptidase A activities of BMMCs derived from GalNAc4S-6ST-null mice were lower than those activities of BMMCs derived from wild-type mice, although mRNA expression of these mast cell proteases was not altered. Disaccharide compositions of heparan sulfate/heparin contained in the mast cells derived from BMMCs in the presence of stem cell factor were much different from those of heparan sulfate/heparin in BMMCs but did not differ significantly between wild-type mice and GalNAc4S-6ST-null mice. These observations suggest that CS containing GalNAc(4,6-SO(4)) residues in BMMCs may contribute to retain the active proteases in the granules of BMMCs but not for the maturation of BMMCs into connective tissue-type mast cells.
巻・号 285(27)
ページ 20793-805
公開日 2010-7-2
DOI 10.1074/jbc.M109.084749
PII S0021-9258(20)57366-3
PMID 20439988
PMC PMC2898370
MeSH Acetylgalactosamine / analogs & derivatives* Acetylgalactosamine / biosynthesis Acetylgalactosamine / chemistry Animals Bone Marrow / enzymology* Bone Marrow / ultrastructure Chondroitin Sulfates / biosynthesis* Chondroitin Sulfates / chemistry DNA / genetics DNA Primers Dermatan Sulfate / biosynthesis* Dermatan Sulfate / chemistry Disaccharides / analysis Exons / genetics Genetic Vectors Glycosaminoglycans / biosynthesis* Mast Cells / enzymology Mast Cells / ultrastructure Mice Microscopy, Electron Peptide Hydrolases / metabolism* Polymerase Chain Reaction RNA, Messenger / genetics* Spleen / enzymology Sulfotransferases / deficiency* Sulfotransferases / genetics
IF 4.238
引用数 25
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞