Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis
Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis
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DOI：
10.1093/emboj/19.5.1010
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发表时间：
2000-03-01
期刊：
影响因子：
11.4
通讯作者：
Fraser, SE
中科院分区：
文献类型：
--
作者：
Rothbächer, U;Laurent, MN;Fraser, SE
蓬乱 (Dsh) 会诱导第二轴，并在被卷曲激活时可移位到膜上；然而，显性失活方法并不支持 Dsh 在原发性亚洲病形成中的作用。我们证明 Dsh 蛋白在胚胎背侧进行翻译后修饰：这种调节的时间和位置表明 Dsh 在非洲爪蟾背腹模式中的作用。为了在 Dsh 的这些特性之间建立功能联系，我们分析了内源性卷曲的影响以及这些特性的 Dsh 结构域依赖性。非洲爪蟾卷曲体磷酸化 Xdsh 并将其易位到膜上，无论其异位轴诱导能力如何，表明易位不足以诱导轴。 Dsh 缺失分析表明轴诱导能力并不与 Xdsh 膜关联分离。 DIX 区域和 DEP 结构域 N 末端的短段对于轴诱导是必需的，而 DEP 区域是 Dsh 膜结合及其磷酸化所必需的。此外，Dsh 在胚胎中形成同聚复合物，表明多聚化对其正常功能很重要。
Dishevelled (Dsh) induces a secondary axis and can translocate to the membrane when activated by Frizzleds; however, dominant-negative approaches have not supported a role for Dsh in primary asis formation. We demonstrate that the Dsh protein is post-translationally modified at the dorsal side of the embryo: timing and position of this regulation suggests a role of Dsh in dorsal-ventral patterning in Xenopus. To create functional links between these properties of Dsh we analyzed the influence of endogenous Frizzleds and the Dsh domain dependency for these characteristics. Xenopus Frizzleds phosphorylate and translocate Xdsh to the membrane irrespective of their differential ectopic axes inducing abilities, showing that translocation is insufficient for axis induction. Dsh deletion analysis revealed that axis inducing abilities did not segregate with Xdsh membrane association. The DIX region and a short stretch at the N-terminus of the DEP domain are necessary for axis induction while the DEP region is required for Dsh membrane association and its phosphorylation, In addition, Dsh forms homomeric complexes in embryos suggesting that multimerization is important for its proper function.