Abstract
Heparan sulfate (HS) regulates the activity of various ligands and is involved in molecular recognition events on the cell surface and in the extracellular matrix. Specific binding of HS to different ligand proteins depends on the sulfation pattern of HS. For example, the interaction between antithrombin and a particular 3-O sulfated HS motif is thought to modulate blood coagulation. However, a recent study of mice defective for this modification suggested that 3-O sulfation plays other biological roles. Here, we show that Drosophila melanogaster HS 3-O sulfotransferase-b (Hs3st-B), which catalyzes HS 3-O sulfation, is a novel component of the Notch pathway. Reduction of Hs3st-B function by transgenic RNA interference compromised Notch signaling, producing neurogenic phenotypes. We also show that levels of Notch protein on the cell surface were markedly decreased by loss of Hs3st-B. These findings suggest that Hs3st-B is involved in Notch signaling by affecting stability or intracellular trafficking of Notch protein.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Base Sequence / genetics
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Cell Membrane / genetics
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Cell Membrane / metabolism
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Down-Regulation / genetics
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Drosophila Proteins / genetics
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Drosophila Proteins / isolation & purification
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / embryology
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Extracellular Matrix / genetics
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Extracellular Matrix / metabolism
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Gene Expression Regulation, Developmental / genetics
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Heparitin Sulfate / metabolism*
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Intracellular Membranes / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Phenotype
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Protein Binding / genetics
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Protein Transport / genetics
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RNA Interference
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Receptors, Notch
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Sulfotransferases / genetics
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Sulfotransferases / isolation & purification
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Sulfotransferases / metabolism*
Substances
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DNA, Complementary
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Drosophila Proteins
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Membrane Proteins
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N protein, Drosophila
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Receptors, Notch
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Heparitin Sulfate
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Sulfotransferases
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heparitin sulfotransferase