Heparan sulfate 6-O-sulfotransferase is essential for muscle development in zebrafish

被引:64
作者
Bink, RJ
Habuchi, H
Lele, Z
Dolk, E
Joore, J
Rauch, GJ
Geisler, R
Wilson, SW
den Hertog, J
Kimata, K
Zivkovic, D
机构
[1] Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands
[2] Aichi Med Univ, Inst Mol Sci Med, Aichi 4801195, Japan
[3] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England
[4] Max Planck Inst Entwicklungsbiol, Abt Genet 3, D-72076 Tubingen, Germany
关键词
D O I
10.1074/jbc.M213124200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Heparan sulfate proteoglycans function in development and disease. They consist of a core protein with attached heparan sulfate chains that are altered by a series of carbohydrate-modifying enzymes and sulfotransferases. Here, we report on the identification and characterization of a gene encoding zebrafish heparan sulfate 6-O-sulfotransferase (hs6st) that shows high homology to other heparan sulfate 6-O-sulfotransferases. When expressed as a fusion protein in cultured cells, the protein shows specific 6-O-sulfotransferase activity and preferentially acts on the iduronosyl N-sulfoglycosamine. In the developing embryo, hs6st is expressed in the brain, the somites, and the fins; the same structures that were affected upon morpholino-mediated functional knockdown. Morpholino injections significantly inhibited 6-O- but not 2-O-sulfation as assessed by HPLC. Morphants display disturbed somite specification independent of the somite oscillator mechanism and have impaired muscle differentiation. In conclusion, our results show that transfer of sulfate to specific positions on glycosaminoglycans is essential for muscle development.
引用
收藏
页码:31118 / 31127
页数:10
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