Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase

Keisuke Kamimura, John M. Rhodes, Ryu Ueda, Melissa McNeely, Deepak Shukla, Koji Kimata, Patricia G. Spear, Nicholas W. Shworak, Hiroshi Nakato

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1069-1079
Number of pages11
JournalJournal of Cell Biology
Volume166
Issue number7
DOIs
StatePublished - Sep 27 2004

Keywords

  • 3-O sulfation
  • Drosophila
  • Heparan sulfate proteoglycan
  • Notch signaling
  • Transgenic RNAi

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