Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase.
Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase.
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DOI：
10.1083/jcb.200403077
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发表时间：
2004-09-27
影响因子：
7.8
通讯作者：
Nakato, Hiroshi
中科院分区：
文献类型：
--
作者：
Kamimura, Keisuke;Rhodes, John M;Ueda, Ryu;McNeely, Melissa;Shukla, Deepak;Kimata, Koji;Spear, Patricia G;Shworak, Nicholas W;Nakato, Hiroshi
硫酸乙酰肝素（HS）调节各种配体的活性，并参与细胞表面和细胞外基质中的分子识别事件。HS与不同配体蛋白的特异性结合取决于HS的硫酸化模式。例如，抗凝血酶和特定的3-O硫酸化HS基序之间的相互作用被认为调节血液凝固。然而，最近对这种修饰缺陷的小鼠的研究表明，3-O硫酸化起着其他生物学作用。在这里，我们表明，果蝇HS 3-O磺基转移酶-B（Hs 3st-B），催化HS 3-O硫酸化，是一个新的组成部分的Notch途径。通过转基因RNA干扰降低Hs 3st-B功能损害Notch信号传导，产生神经原性表型。我们还表明，细胞表面上的Notch蛋白的水平显着降低了Hs 3st-B的损失。这些发现表明Hs 3st-B通过影响Notch蛋白的稳定性或细胞内运输参与Notch信号传导。
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.