Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Development. 2009 Dec;136(24):4083-8. doi: 10.1242/dev.032524. Epub 2009 Nov 11.
Secreted Frizzled-related proteins (sFRPs) are thought to negatively modulate Wnt signalling. Although Wnt proteins are thought to diffuse extracellularly and act as morphogens, little is known about the diffusibility of either Wnts or sFRPs. Here we show that Frzb and Crescent (Cres), which are members of the sFRP family, have the ability to regulate the diffusibility and signalling areas of the Wnt ligands Wnt8 and Wnt11. We found, using the Xenopus embryo, that Wnts do not diffuse effectively, whereas Frzb and Cres spread very widely. Interestingly, Frzb and Cres substantially promoted the diffusion of Wnt8 and Wnt11 through extracellular interactions. Importantly, we show that Wnt8 conveyed by sFRPs can activate canonical Wnt signalling despite the function of sFRPs as Wnt inhibitors, suggesting a novel regulatory system for Wnts by sFRPs.
分泌型卷曲相关蛋白（sFRP）被认为可负向调节 Wnt 信号通路。虽然 Wnt 蛋白被认为可以在细胞外扩散并充当形态发生素，但对于 Wnt 或 sFRP 的扩散性知之甚少。在这里，我们发现 Frzb 和 Crescent（Cres），它们是 sFRP 家族的成员，具有调节 Wnt 配体 Wnt8 和 Wnt11 的扩散性和信号区域的能力。我们发现，在 Xenopus 胚胎中，Wnt 不能有效地扩散，而 Frzb 和 Cres 则广泛传播。有趣的是，Frzb 和 Cres 通过细胞外相互作用大大促进了 Wnt8 和 Wnt11 的扩散。重要的是，我们表明，sFRP 传递的 Wnt8 可以激活经典的 Wnt 信号通路，尽管 sFRP 作为 Wnt 抑制剂发挥作用，这表明 sFRP 对 Wnt 的一种新的调节系统。
