Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF
Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF
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DOI：
10.1016/j.cell.2004.11.051
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发表时间：
2005-01-28
期刊：
影响因子：
64.5
通讯作者：
Aizawa, S
中科院分区：
文献类型：
--
作者：
Yamamoto, A;Nagano, T;Aizawa, S
头部形成需要在脊椎动物早期胚胎发育过程中同时抑制多个尾化信号。我们发现了一种新的拮抗剂，它能拮抗Wnt和成纤维细胞生长因子的头部形成信号，它在内质网(ER)中自主发挥细胞的作用。Shisa在非洲爪蛙的预期头部外胚层和Spemann组织器中特异表达。在非洲爪哇胚胎和细胞系中过表达shisa抑制了Wnt和Fgf信号转导。Shisa功能的丧失使神经外胚层对Wnt信号敏感，并抑制了原肠形成过程中的头部形成。SHISA与内质网中未成熟的Wnt受体Frizzled型和成纤维细胞生长因子受体相互作用，并抑制它们的翻译后成熟和向细胞表面的转运。综上所述，这些发现表明，ShISA是一种新的分子，它通过调节尾化因子受体的建立来控制头部的形成。
Head formation requires simultaneous inhibition of multiple caudalizing signals during early vertebrate embryogenesis. We identified a novel antagonist against Wnt and FGF signaling for head formation, Shisa, which functions cell autonomously in the endoplasmic reticulum (ER). Shisa is specifically expressed in the prospective head ectoderm and the Spemann organizer of Xenopus gastrulae. Overexpression of Shisa inhibited both Wnt and FGF signaling in Xenopus embryos and in a cell line. Loss of Shisa function sensitized the neuroectoderm to Wnt signaling and suppressed head formation during gastrulation. Shisa physically interacted with immature forms of the Wnt receptor Frizzled and the FGF receptor within the ER and inhibited their posttranslational maturation and trafficking to the cell surface. Taken together, these findings indicate that Shisa is a novel molecule that controls head formation by regulating the establishment of the receptors for caudalizing factors.