A zebrafish Notum homolog specifically blocks the Wnt/β-catenin signaling pathway
A zebrafish Notum homolog specifically blocks the Wnt/β-catenin signaling pathway
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DOI：
10.1242/dev.063206
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发表时间：
2012-07-01
期刊：
影响因子：
4.6
通讯作者：
Topczewski, Jacek
中科院分区：
文献类型：
--
作者：
Flowers, G. Parker;Topczewska, Jolanta M.;Topczewski, Jacek
多个发育过程需要严格控制Wnt信号，其错误调节会导致先天性异常和疾病。Glypicans是调节Wnt途径的胞外蛋白。除了与WNTs相互作用外，这些糖磷酰肌醇(GPI)锚定的硫酸乙酰肝素蛋白多糖还与脊椎动物和无脊椎动物中其他几个信号通路的配体结合。在果蝇中，NOTOM是一种分泌的α/β水解酶，通过从细胞表面释放Glypicans来拮抗原型Wnt Wingless(Wg)的信号。对哺乳动物NOTUM的研究表明，在细胞培养中存在靶标特异性的混乱，但NOTOM在脊椎动物发育中的作用尚未被研究。我们的工作表明，斑马鱼Notom 1a是哺乳动物Notom的同源基因，它参与了一个自我调节环，限制了Wnt/β-catenin信号转导。Notom 1a不与Glypical4相互作用，Glypical4是Wnt/平面细胞极性(PCP)途径的重要组成部分。我们的结果表明，Notom在脊椎动物胚胎发育中具有令人惊讶的特殊作用。
Multiple developmental processes require tightly controlled Wnt signaling, and its misregulation leads to congenital abnormalities and diseases. Glypicans are extracellular proteins that modulate the Wnt pathway. In addition to interacting with Wnts, these glycosophosphotidylinositol (GPI)-anchored, heparan-sulfate proteoglycans bind ligands of several other signaling pathways in both vertebrates and invertebrates. In Drosophila, Notum, a secreted alpha/beta-hydrolase, antagonizes the signaling of the prototypical Wnt Wingless (Wg), by releasing glypicans from the cell surface. Studies of mammalian Notum indicate promiscuous target specificity in cell culture, but the role of Notum in vertebrate development has not been studied. Our work shows that zebrafish Notum 1a, an ortholog of mammalian Notum, contributes to a self-regulatory loop that restricts Wnt/beta-catenin signaling. Notum 1a does not interact with Glypican 4, an essential component of the Wnt/planar cell polarity (PCP) pathway. Our results suggest a surprising specific role of Notum in the developing vertebrate embryo.