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.
Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase
D. Shukla's present address is Dept. of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612.
Abbreviations used in this paper: ACV, anterior cross vein; A/P, anterior–posterior; AT, antithrombin; BDGP, Berkeley Drosophila Genome Project; ct, cut; Dl, Delta; dpp, decapentaplegic; dx, deltex; D/V, dorsal–ventral; E(spl)C, Enhancer of split Complex; gD, glycoprotein D; HS, heparan sulfate; HS3ST, HS 3-O sulfotransferase; HSPG, HS proteoglycan; HSV, herpes simplex virus; IR, inverted repeat; kuz, kuzbanian; N, Notch; NECD, extracellular domain of N protein; neur, neuralized; NICD, intracellular domain of N protein; RNAi, RNA interference; sca, scabrous; Ser, Serrate; SMC, sensory organ mother cell; ST, sulfotransferase; Su(H), Suppressor of Hairless; UAS, upstream activating sequence; vg, vestigial; wg, wingless.
Keisuke Kamimura, John M. Rhodes, Ryu Ueda, Melissa McNeely, Deepak Shukla, Koji Kimata, Patricia G. Spear, Nicholas W. Shworak, Hiroshi Nakato; Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase . J Cell Biol 27 September 2004; 166 (7): 1069–1079. doi: https://doi.org/10.1083/jcb.200403077
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