Frizzled receptors bind Wnts

The highly conserved Wnt signaling proteins play critical roles in guiding pattern formation, cell fate decision, and morphogenetic movement during animal development. They bind to the Frizzled (FZD) family of seven-pass transmembrane proteins and initiate at least three different intracellular signaling pathways. Historically they were considered to be family B GPCRs but more recent phylogenetic classifications put them into a class of their own (e.g. Schioth & Fredriksson 2005). FZD members have been demonstrated to signal via Gi/o (Slusarski et al. 1997) but this is not considered to be the primary signaling mechanism for these receptors (Hsieh 2004). Instead they signal through the canonical/beta-catenin pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. The canonical/beta-catenin pathway requires a co-receptor protein known as LDL5 or LDL6 (Tamai et al. 2000). <br>Most Wnt signaling has been attributed to the activation of FZD receptors but there is evidence of FZD-independent signaling (Mikels & Nusse 2006). Much Wnt research has used indirect evidence to infer the involvement of FZD receptors (e.g. Gazit et al. 1999) but there is some direct evidence of Wnt-FZD binding (Hsieh et al. 1999; Mikels & Nusse 2006).

高度保守的Wnt信号蛋白在动物发育过程中，在引导模式形成、细胞命运决定和形态发生运动中发挥着至关重要的作用。它们与七次跨膜蛋白家族的Frizzled（FZD）结合，并启动至少三条不同的细胞内信号通路。历史上，这些蛋白曾被归类为家族B的G蛋白偶联受体（GPCRs），但根据最近的系统发育分类，它们被归入一个独特的类别（例如，Schioth & Fredriksson 2005）。FZD成员已被证实通过Gi/o（Slusarski等，1997）进行信号传递，但这并非这些受体的主要信号机制（Hsieh 2004）。相反，它们通过经典/β-连环蛋白通路、平面细胞极性（PCP）通路和Wnt/钙离子通路进行信号传递。经典/β-连环蛋白通路需要一个共受体蛋白，称为LDL5或LDL6（Tamai等，2000）。大多数Wnt信号被认为是由FZD受体的激活引起的，但有证据表明存在FZD非依赖性信号（Mikels & Nusse 2006）。许多Wnt研究利用间接证据推断FZD受体的参与（例如，Gazit等，1999），但也有一些直接证据表明Wnt与FZD的结合（Hsieh等，1999；Mikels & Nusse 2006）。