Chondroitin 4-O-sulfotransferase-1 regulates the chain length of chondroitin sulfate in co-operation with chondroitin N-acetylgalactosaminyltransferase-2
-
- Tomomi Izumikawa
- Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
-
- Yuka Okuura
- Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
-
- Toshiyasu Koike
- Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
-
- Naoki Sakoda
- Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
-
- Hiroshi Kitagawa
- Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
説明
<jats:p>Previously, we demonstrated that sog9 cells, a murine L cell mutant, are deficient in the expression of C4ST (chondroitin 4-O-sulfotransferase)-1 and that they synthesize fewer and shorter CS (chondroitin sulfate) chains. These results suggested that C4ST-1 regulates not only 4-O-sulfation of CS, but also the length and amount of CS chains; however, the mechanism remains unclear. In the present study, we have demonstrated that C4ST-1 regulates the chain length and amount of CS in co-operation with ChGn-2 (chondroitin N-acetylgalactosaminyltransferase 2). Overexpression of ChGn-2 increased the length and amount of CS chains in L cells, but not in sog9 mutant cells. Knockdown of ChGn-2 resulted in a decrease in the amount of CS in L cells in a manner proportional to ChGn-2 expression levels, whereas the introduction of mutated C4ST-1 or ChGn-2 lacking enzyme activity failed to increase the amount of CS. Furthermore, the non-reducing terminal 4-O-sulfation of N-acetylgalactosamine residues facilitated the elongation of CS chains by chondroitin polymerase consisting of chondroitin synthase-1 and chondroitin-polymerizing factor. Overall, these results suggest that the chain length of CS is regulated by C4ST-1 and ChGn-2 and that the enzymatic activities of these proteins play a critical role in CS elongation.</jats:p>
収録刊行物
-
- Biochemical Journal
-
Biochemical Journal 434 (2), 321-331, 2011-02-11
Portland Press Ltd.