Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum
Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum
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DOI：
10.1074/jbc.m200187200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
--
作者：
Tanaka, K;Kitagawa, Y;Kadowaki, T
Wnt是一类富含半胱氨酸的分泌性糖蛋白家族，在多细胞生物中控制着细胞的命运和行为。果蝇Wnt家族成员无翅蛋白（Wingless，Wg）的N-糖基化功能在缺少编码内质网多跨膜蛋白的果蝇体节极性基因porcupine（pore）的情况下受到损伤。相反，孔的异位表达刺激内源性和外源性表达的Wg的N-糖基化。ER中Wg的N-糖基化发生在后分泌期，而在二硫苏糖醇存在下，其有效地发生在后分泌期。因此，Wg的共翻译二硫键形成与寡糖基转移酶复合物的N-糖基化竞争。Pore结合Wg的N-末端24-氨基酸结构域（残基83-106），其在Wnt家族中高度保守并刺激周围位点的N-糖基化。孔对于果蝇Wnt-3/5在胚胎和培养细胞中的加工也是必需的。因此，Pore结合Wnt家族的N-末端特异性结构域，并可能通过酰化将它们锚定在ER膜上，从而刺激其翻译后N-糖基化。
Wnt is a family of cysteine-rich secreted glycoproteins, which controls the fate and behavior of the cells in multicellular organisms. In the absence of Drosophila segment polarity gene porcupine (pore), which encodes an endoplasmic reticulum (ER) multispanning transmembrane protein, the N-glycosylation of Wingless (Wg), one of Drosophila Wnt family, is impaired. In contrast, the ectopic expression of pore stimulates the N-glycosylation of both endogenously and exogenously expressed Wg. The N-glycosylation of Wg in the ER occurs posttranslationally, while in the presence of dithiothreitol, it efficiently occurs cotranslationally. Thus, the cotranslational disulfide bond formation of Wg competes with the N-glycosylation by an oligosaccharyl transferase complex. Pore binds the N-terminal 24-amino acid domain (residues 83-106) of Wg, which is highly conserved in the Wnt family and stimulates the N-glycosylation at surrounding sites. Pore is also necessary for the processing of Drosophila Wnt-3/5 in both embryos and cultured cells. Thus, Pore binds the N-terminal specific domain of the Wnt family and stimulates its posttranslational N-glycosylation by anchoring them at the ER membrane possibly through acylation.