Neural-specific α3-fucosylation of N-linked glycans in the Drosophila embryo requires fucosyltransferase A and influences developmental signaling associated with O-glycosylation.
Neural-specific α3-fucosylation of N-linked glycans in the Drosophila embryo requires fucosyltransferase A and influences developmental signaling associated with O-glycosylation.
复制标题
果蝇胚胎中 N 连接聚糖的神经特异性 α3-岩藻糖基化需要岩藻糖基转移酶 A 并影响与 O-糖基化相关的发育信号。
DOI：
10.1093/glycob/cwq119
复制
发表时间：
2010
期刊：
影响因子：
4.3
通讯作者：
Tiemeyer,Michael
中科院分区：
文献类型：
--
作者：
Rendić,Dubravko;Sharrow,Mary;Katoh,Toshihiko;Overcarsh,Bryan;Nguyen,Khoi;Kapurch,Joseph;Aoki,Kazuhiro;Wilson,IainBH;Tiemeyer,Michael
将岩藻糖 (Fuc) 添加到糖蛋白 N 连接聚糖上或直接以 O 连接形式添加到 Ser/Thr 残基上，可调节特定的细胞间相互作用和细胞信号转导事件。脊椎动物和无脊椎动物将Fuc以α6-键连接到N-聚糖的还原性末端N-乙酰葡糖胺残基上。在果蝇和其他无脊椎动物中，Fuc 也可以以 α3-键添加到相同的残基上。这些二岩藻糖基化的 N-聚糖可被抗辣根过氧化物酶 (抗 HRP) 抗血清识别，为昆虫神经组织提供了完善的标记。为了了解组织特异性聚糖表达的机制和后果，我们鉴定了一种在果蝇胚胎中产生抗 HRP 表位的单一 α3-岩藻糖基转移酶 (FucTA)。 FucTA 转录物在时间和空间上仅限于表达抗 HRP 表位的细胞，并且在缺乏神经 α3-岩藻糖基化的突变体中缺失。 FucTA 的转基因表达（而非任何其他候选 α3-岩藻糖基转移酶）拯救了该突变体胚胎神经系统中的抗 HRP 表位。过表达 FucTA 的果蝇胚胎 N-聚糖的质谱表征证实，该酶确实负责体内二岩藻糖基化聚糖的生物合成。 FucTA 在幼虫翅盘中的异位表达会产生轻微的翅切迹，而 FucTA 在早期分化神经元中的异时性、全神经表达会产生神经源性和细胞迁移表型；后一种效应与胚胎中GDP-Fuc水平降低有关，并表明岩藻糖基化资源向N-聚糖岩藻糖基化的转移对与O-岩藻糖基化相关的发育信号传导有影响。
Addition of fucose (Fuc) to glycoproteinN-linked glycans or in O-linkage directly to Ser/Thr residues modulates specific cell–cell interactions and cell signaling events. Vertebrates and invertebrates add Fuc in α6-linkage to the reducing terminalN-acetylglucosamine residue ofN-glycans. InDrosophilaand other invertebrates, Fuc can also be added in α3-linkage to the same residue. These difucosylatedN-glycans are recognized by anti-horseradish peroxidase (anti-HRP) antisera, providing a well-established marker for insect neural tissue. To understand the mechanisms and consequences of tissue-specific glycan expression, we identified a single α3-fucosyltransferase (FucTA) that produces the anti-HRP epitope inDrosophilaembryos. FucTA transcripts are temporally and spatially restricted to cells that express the anti-HRP epitope and are missing in a mutant that lacks neural α3-fucosylation. Transgenic expression of FucTA, but not of any other candidate α3-fucosyltransferase, rescues the anti-HRP epitope in the embryonic nervous system of this mutant. Mass spectrometric characterization of theN-glycans ofDrosophilaembryos overexpressing FucTA confirms that this enzyme is indeed responsible for the biosynthesis of difucosylated glycans in vivo. Whereas ectopic expression of FucTA in the larval wing disc produces mild wing notching, the heterochronic, pan-neural expression of FucTA in early differentiating neurons generates neurogenic and cell migration phenotypes; this latter effect is associated with reduced GDP-Fuc levels in the embryo and indicates that the diversion of fucosylation resources towards fucosylation ofN-glycans has an impact on developmental signaling associated with O-fucosylation.