Heparan sulfate 6-O-sulfotransferase is essential for muscle development in zebrafish
- Bink, R.J., Habuchi, H., Lele, Z., Dolk, E., Joore, J., Rauch, G.J., Geisler, R., Wilson, S.W., den Hertog, J., Kimata, K., and Zivkovic, D.
- The Journal of biological chemistry 278(33): 31118-31127 (Journal)
- Registered Authors
- den Hertog, Jeroen, Geisler, Robert, Jongejan-Zivkovic, Dana, Joore, Jos, Lele, Zsolt, Rauch, Gerd-Jörg, Wilson, Steve
- MeSH Terms
- Amino Acid Sequence
- Cell Differentiation
- Gene Expression Regulation, Developmental
- Gene Expression Regulation, Enzymologic
- Heparan Sulfate Proteoglycans/metabolism*
- Molecular Sequence Data
- Muscle, Skeletal/cytology
- Muscle, Skeletal/embryology*
- Muscle, Skeletal/enzymology*
- Oligonucleotides, Antisense/pharmacology
- 12782624 Full text @ J. Biol. Chem.
Bink, R.J., Habuchi, H., Lele, Z., Dolk, E., Joore, J., Rauch, G.J., Geisler, R., Wilson, S.W., den Hertog, J., Kimata, K., and Zivkovic, D. (2003) Heparan sulfate 6-O-sulfotransferase is essential for muscle development in zebrafish. The Journal of biological chemistry. 278(33):31118-31127.
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 that shows high homology to other heparansulfate 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 glycosaminglycans is essential for muscle development.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes