Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation.
Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation.
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DOI：
10.1016/j.devcel.2015.02.014
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发表时间：
2015-03-23
影响因子：
11.8
通讯作者：
He, Xi
中科院分区：
文献类型：
--
作者：
Zhang, Xinjun;Cheong, Seong-Moon;Amado, Nathalia G.;Reis, Alice H.;MacDonald, Bryan T.;Zebisch, Matthias;Jones, E. Yvonne;Abreu, Jose Garcia;He, Xi
分泌的Wnt形态发生素对于胚胎发生和体内平衡是必需的，并且需要脂质/棕榈油酸酯修饰以用于受体结合和活性。Notum是属于α/β水解酶超家族的分泌型Wnt拮抗剂，但其作用机制和在脊椎动物胚胎发生中的作用尚未完全了解。在这里，我们报告Notum水解的Wnt palmitoleoylate加合物细胞外，导致在失活的Wnt蛋白，形成氧化的寡聚体不能受体结合。因此Notum是一种Wnt脱酰基酶，棕榈油酰化是Wnt结构保持其活性单体构象的必要条件。Notum在非洲爪蟾的幼稚外胚层和神经板中表达，并且是神经和头部诱导所需的。这些研究结果表明，不同的机制Wnt失活的Tiki蛋白酶的组织者和Notum脱酰基酶在假定的神经外胚层编排脊椎动物的大脑发育。
Secreted Wnt morphogens are essential for embryogenesis and homeostasis, and require a lipid/palmitoleoylate modification for receptor binding and activity. Notum is a secreted Wnt antagonist that belongs to the α/β hydrolase superfamily, but its mechanism of action and roles in vertebrate embryogenesis are not fully understood. Here we report that Notum hydrolyzes the Wnt palmitoleoylate adduct extracellularly, resulting in inactivated Wnt proteins that form oxidized oligomers incapable of receptor binding. Thus Notum is a Wnt deacylase, and palmitoleoylation is obligatory for the Wnt structure that maintains its active monomeric conformation. Notum is expressed in naïve ectoderm and neural plate in Xenopus and is required for neural and head induction. These findings suggest that distinct mechanisms of Wnt inactivation by the Tiki protease in the Organizer and the Notum deacylase in presumptive neuroectoderm orchestrate vertebrate brain development.
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影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
2.7
作者：
Herr, Patrick;Basler, Konrad
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影响因子：
4
作者：
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通讯作者：
Filmus, Jorge
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19
作者：
Beckett, Karen;Franch-Marro, Xavier;Vincent, Jean-Paul
通讯作者：
Vincent, Jean-Paul
影响因子：
12.3
作者：
Filmus J;Capurro M;Rast J
通讯作者：
Rast J