title: Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1.
abstract: Recently, it has been shown that a deficiency in ChGn-1 (chondroitin N-acetylgalactosaminyltransferase-1) reduced the numbers of CS (chondroitin sulfate) chains, leading to skeletal dysplasias in mice. Although these results indicate that ChGn-1 regulates the number of CS chains, the mechanism mediating this regulation is not clear. ChGn-1 is thought to initiate CS biosynthesis by transferring the first GalNAc (N-acetylgalactosamine) to the tetrasaccharide in the protein linkage region of CS. However, in vitro chondroitin polymerization does not occur on the non-reducing terminal GalNAc-linkage pentasaccharide structure. In the present study we show that several different heteromeric enzyme complexes composed of different combinations of four chondroitin synthase family members synthesized more CS chains when a GalNAc-linkage pentasaccharide structure with a non-reducing terminal 4-O-sulfation was the CS acceptor. In addition, C4ST-2 (chondroitin 4-O-sulfotransferase-2) efficiently transferred sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 4 of non-reducing terminal GalNAc-linkage residues, and the number of CS chains was regulated by the expression levels of C4ST-2 and of ChGn-1. Taken together, the results of the present study indicate that C4ST-2 plays a key role in regulating levels of CS synthesized via ChGn-1.
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Izumikawa
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Koike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism; D000818:Animals; D002809:Chondroitin Sulfates / Q000096:biosynthesis*; D007739:L Cells; D051379:Mice; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism / Q000502:physiology*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D000116:Acetylgalactosamine; D002809:Chondroitin Sulfates; D017350:N-Acetylgalactosaminyltransferases; D015238:Sulfotransferases; C569943:chondroitin N-acetylgalactosaminyltransferase-1, mouse; C557901:Chst11 protein, mouse; D000097811:Carbohydrate Sulfotransferases; C569944:chondroitin 4-O-sulfotransferase 2, mouse; C438013:dermatan-4-sulfotransferase-1; C019893:chondroitin 4-sulfotransferase