PUBLICATION
Selective yolk deposition and mannose phosphorylation of lysosomal glycosidases in zebrafish
- Authors
- Fan, X., Klein, M., Flanagan-Steet, H.R., and Steet, R.
- ID
- ZDB-PUB-100826-12
- Date
- 2010
- Source
- The Journal of biological chemistry 285(43): 32946-32953 (Journal)
- Registered Authors
- Fan, Xiang, Flanagan-Steet, Heather, Steet, Richard
- Keywords
- Lysosomal storage disease, Lysosomes, Oligosaccharide, Protein turnover, Zebra fish, acid alpha-glucosidase, alpha-mannosidase, mannose 6-phosphate
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Enzyme Inhibitors/pharmacology
- Glycoside Hydrolases/genetics
- Glycoside Hydrolases/metabolism*
- Humans
- Lysosomes/enzymology*
- Lysosomes/genetics
- Mannose/genetics
- Mannose/metabolism*
- Mannosephosphates/genetics
- Mannosephosphates/metabolism
- Phosphorylation/drug effects
- Phosphorylation/physiology
- Swainsonine/pharmacology
- Yolk Sac/embryology
- Yolk Sac/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- PubMed
- 20729204 Full text @ J. Biol. Chem.
Citation
Fan, X., Klein, M., Flanagan-Steet, H.R., and Steet, R. (2010) Selective yolk deposition and mannose phosphorylation of lysosomal glycosidases in zebrafish. The Journal of biological chemistry. 285(43):32946-32953.
Abstract
The regulation and function of lysosomal hydrolases during yolk consumption and embryogenesis in zebrafish are poorly understood. In an effort to better define the lysosomal biochemistry of this organism, we analyzed the developmental expression, biochemical properties and function of several glycosidases in zebrafish eggs, embryos and adult tissues. Our results demonstrated that the specific activity of most enzymes increases during embryogenesis, likely reflecting a greater need for turnover within the embryo as yolk-derived nutrients are depleted. Analysis of glycosidase activity in zebrafish and medaka eggs revealed selective deposition of enzymes required for the degradation of N-linked glycans, including an abundance of acidic mannosidases. Treatment of zebrafish embryos with the alpha-mannosidase inhibitor swainsonine resulted in the accumulation of glycosylated vitellogenin fragments, demonstrated a function for maternally deposited acid alpha-mannosidase in yolk consumption. Surprisingly, we also found that, unlike mammals, acid alpha-glucosidase from zebrafish and medaka does not appear to be modified with mannose 6-phosphate residues. We further showed these residues were not acquired on human acid alpha-glucosidase when expressed in zebrafish embryos, suggesting unique differences in the ability of the human and zebrafish N-acetylglucosamine-1-phosphotransferase to recognize and modify certain lysosomal glycosidases. Together, these results provide novel insight into the role of acidic glycosidases during yolk utilization and the evolution of the mannose 6-phosphate targeting system in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping