Wehrli M, Dougan S T, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S
University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Nature. 2000 Sep 28;407(6803):527-30. doi: 10.1038/35035110.
The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.
分泌分子的Wnt家族在脊椎动物和无脊椎动物发育过程中的细胞命运决定和形态发生中发挥作用（参考文献1中有综述）。果蝇的无翅基因（Wingless）是该家族的创始成员，其信号转导级联反应的许多组成部分已被确定，包括卷曲蛋白（Frizzled）类受体。但是，无翅信号在细胞膜上的接收和转导机制尚未完全了解。在这里，我们描述了一个在果蝇所有无翅信号传导事件中都必需的基因。我们表明，箭基因（arrow）的功能在接收无翅信号输入的细胞中至关重要，并且它在散乱蛋白（Dishevelled）的上游起作用。箭基因编码一种单次跨膜蛋白，这表明它可能是与卷曲蛋白类蛋白形成的受体复合物的一部分。箭蛋白是一种低密度脂蛋白（LDL）受体相关蛋白（LRP），与小鼠和人类的LRP5和LRP6具有显著的同源性。因此，我们的数据表明该LRP亚家族在无翅/ Wnt信号接收中具有新的保守功能。
