| First Author | Izumikawa T | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 9 | Pages | 5438-48 |
| PubMed ID | 25568321 | Mgi Jnum | J:219334 |
| Mgi Id | MGI:5620532 | Doi | 10.1074/jbc.M114.603266 |
| Citation | Izumikawa T, et al. (2015) GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate) Is the Preferred Substrate for Chondroitin N-Acetylgalactosaminyltransferase-1. J Biol Chem 290(9):5438-48 |
| abstractText | A deficiency in chondroitin N-acetylgalactosaminyltransferase-1 (ChGn-1) was previously shown to reduce the number of chondroitin sulfate (CS) chains, leading to skeletal dysplasias in mice, suggesting that ChGn-1 regulates the number of CS chains for normal cartilage development. Recently, we demonstrated that 2-phosphoxylose phosphatase (XYLP) regulates the number of CS chains by dephosphorylating the Xyl residue in the glycosaminoglycan-protein linkage region of proteoglycans. However, the relationship between ChGn-1 and XYLP in controlling the number of CS chains is not clear. In this study, we for the first time detected a phosphorylated tetrasaccharide linkage structure, GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate), in ChGn-1(-/-) growth plate cartilage but not in ChGn-2(-/-) or wild-type growth plate cartilage. In contrast, the truncated linkage tetrasaccharide GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl was detected in wild-type, ChGn-1(-/-), and ChGn-2(-/-) growth plate cartilage. Consistent with the findings, ChGn-1 preferentially transferred N-acetylgalactosamine to the phosphorylated tetrasaccharide linkage in vitro. Moreover, ChGn-1 and XYLP interacted with each other, and ChGn-1-mediated addition of N-acetylgalactosamine was accompanied by rapid XYLP-dependent dephosphorylation during formation of the CS linkage region. Taken together, we conclude that the phosphorylated tetrasaccharide linkage is the preferred substrate for ChGn-1 and that ChGn-1 and XYLP cooperatively regulate the number of CS chains in growth plate cartilage. |
