Non-acylated Wnts Can Promote Signaling.
Non-acylated Wnts Can Promote Signaling.
复制标题
非酰化 Wnt 可以促进信号传导。
DOI：
10.1016/j.celrep.2018.12.104
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Lemmon,MarkA
中科院分区：
文献类型：
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作者：
Speer,KelseyF;Sommer,Anselm;Tajer,Benjamin;Mullins,MaryC;Klein,PeterS;Lemmon,MarkA
Wnt是一个由19个细胞外配体组成的家族，在后生动物胚胎发生和整个成年期调节细胞命运、增殖和迁移。Wnt在保守的丝氨酸处被后酰化，并结合卷曲（FZD）七次跨膜受体的胞外富含半胱氨酸结构域（CRD）。虽然晶体结构表明，酰化是必不可少的Wnt结合FZD，我们在这里显示，几个Wnt可以促进信号在非洲爪蟾和斑马鱼胚胎，以及在体外细胞培养模型，没有酰化。非酰化Wnt以与野生型对应物相似的水平表达，并保留CRD结合。相比之下，我们发现某些其他的Wnt确实需要酰化才能在Xenopus胚胎中发挥生物活性，尽管不一定是FZD结合。我们的数据表明，Wnt活性的酰化依赖性是特定的。他们进一步表明，酰化可能是配体-受体选择性方面的基础和/或控制Wnt功能的其他方面。
Wnts are a family of 19 extracellular ligands that regulate cell fate, proliferation, and migration during metazoan embryogenesis and throughout adulthood. Wnts are acylated post-translationally at a conserved serine and bind the extracellular cysteine-rich domain (CRD) of Frizzled (FZD) seven-pass transmembrane receptors. Although crystal structures suggest that acylation is essential for Wnt binding to FZDs, we show here that several Wnts can promote signaling inXenopus laevisandDanio rerioembryos, as well as in anin vitrocell culture model, without acylation. The non-acylated Wnts are expressed at levels similar to wild-type counterparts and retain CRD binding. By contrast, we find that certain other Wnts do require acylation for biological activity inXenopusembryos, although not necessarily for FZD binding. Our data argue that acylation dependence of Wnt activity is context specific. They further suggest that acylation may underlie aspects of ligand-receptor selectivity and/or control other aspects of Wnt function.