Waxman Joshua S, Hocking Anne M, Stoick Cristi L, Moon Randall T
Molecular and Cellular Biology Program, University of Washington School of Medicine, Seattle, WA 98195, USA.
Development. 2004 Dec;131(23):5909-21. doi: 10.1242/dev.01520.
Wnt signaling pathways in vertebrates use the phosphoprotein Dishevelled (Dvl). The cellular responses to Wnt signaling may in part be modulated by Dvl-associated proteins, including Dapper (Dpr). We have cloned and characterized the zebrafish Dpr paralogs Dpr1 and Dpr2. Loss-of-function studies reveal that endogenous Dpr1 but not Dpr2 is required to enhance Wnt/beta-catenin activity in zebrafish embryos that are hypomorphic for Wnt8. Conversely, Dpr2 but not Dpr1 is required for normal convergence extension movements in embryos that are hypomorphic for Stbm or Wnt11, supporting a functional interaction of Dpr2 with Wnt/Ca2+-PCP signaling. In gain-of-function experiments, Dpr1 but not Dpr2 induces Wnt/beta-catenin target genes. Dpr1 synergizes with zebrafish Dvl2, and with the Dvl-interacting kinases CK1epsilon, Par1 and CK2, in activating target genes. We conclude that two Dvl-associated paralogs, Dpr1 and Dpr2, participate in distinct Wnt-dependent developmental processes.
脊椎动物中的Wnt信号通路使用磷蛋白散乱蛋白（Dvl）。细胞对Wnt信号的反应可能部分受到与Dvl相关的蛋白质的调节，包括Dapper（Dpr）。我们已经克隆并鉴定了斑马鱼Dpr的旁系同源物Dpr1和Dpr2。功能丧失研究表明，在Wnt8功能减弱的斑马鱼胚胎中，增强Wnt/β-连环蛋白活性需要内源性Dpr1而不是Dpr2。相反，在Stbm或Wnt11功能减弱的胚胎中，正常的汇聚延伸运动需要Dpr2而不是Dpr1，这支持了Dpr2与Wnt/Ca2+-平面细胞极性（PCP）信号的功能相互作用。在功能获得实验中，Dpr1而不是Dpr2诱导Wnt/β-连环蛋白靶基因。Dpr1与斑马鱼Dvl2以及与Dvl相互作用的激酶CK1εpsilon、Par1和CK2协同激活靶基因。我们得出结论，两个与Dvl相关的旁系同源物Dpr1和Dpr2参与了不同的Wnt依赖性发育过程。
