Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling.
Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling.
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O-核糖基转移酶1对Notch信号传导的伴侣蛋白和糖基转移酶活性的贡献。
DOI：
10.1186/1741-7007-6-1
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发表时间：
2008-01-14
期刊：
影响因子：
5.4
通讯作者：
Irvine, Kenneth D.
中科院分区：
文献类型：
--
作者：
Okajima, Tetsuya;Reddy, B. V. V. G.;Matsuda, Tsukasa;Irvine, Kenneth D.
O-fucosyltransferase1（OFUT1）是Notch信号传导所必需的一种保守的ER蛋白。OFUT1糖基化EGF结构域，然后可以通过N-乙酰葡糖胺转移酶Fringe进一步修饰。OFUT 1还具有促进Notch折叠和分泌的伴侣活性。在这里，我们调查这些活动在果蝇Notch信号各自的贡献。我们发现，表达的异构体缺乏岩藻糖基转移酶活性，Ofut1R245A，拯救Ofut1胚胎神经发生的要求。缺乏对0-岩藻糖基化的需求进一步得到Gmd突变体中缺乏胚胎表型的支持，其缺乏所有形式的岩藻糖基化。通过表征仅表达Ofut 1R245 A的细胞克隆来评估成虫发育期间对O-岩藻糖的需求。这些克隆表型边缘突变体克隆，表明不存在O-岩藻糖在功能上等同于不存在延长的O-岩藻糖。我们的研究结果表明，Notch不需要O-岩藻糖基化的条纹独立的Notch信号在果蝇; OFUT1的伴侣活性是足够的功能性Notch的产生。
O-fucosyltransferase1 (OFUT1) is a conserved ER protein essential for Notch signaling. OFUT1 glycosylates EGF domains, which can then be further modified by the N-acetylglucosaminyltransferase Fringe. OFUT1 also possesses a chaperone activity that promotes the folding and secretion of Notch. Here, we investigate the respective contributions of these activities to Notch signaling in Drosophila. We show that expression of an isoform lacking fucosyltransferase activity, Ofut1R245A, rescues the requirement for Ofut1 in embryonic neurogenesis. Lack of requirement for O-fucosylation is further supported by the absence of embryonic phenotypes in Gmd mutants, which lack all forms of fucosylation. Requirements for O-fucose during imaginal development were evaluated by characterizing clones of cells expressing only Ofut1R245A. These clones phenocopy fringe mutant clones, indicating that the absence of O-fucose is functionally equivalent to the absence of elongated O-fucose. Our results establish that Notch does not need to be O-fucosylated for fringe-independent Notch signaling in Drosophila; the chaperone activity of OFUT1 is sufficient for the generation of functional Notch.
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