Wingless transduction by the Frizzled and Frizzled2 proteins of Drosophila.
Wingless transduction by the Frizzled and Frizzled2 proteins of Drosophila.
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发表时间：
1999-12
期刊：
影响因子：
4.6
通讯作者：
Chiann-mun Chen;G. Struhl
中科院分区：
文献类型：
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作者：
Chiann-mun Chen;G. Struhl
Wg蛋白是Wnt分泌蛋白家族的创始成员，在动物发育过程中起着重要的组织作用。果蝇Fz和Fz2是Frizzled七通道跨膜蛋白家族的两个成员，它们可以与Wg结合，是Wg的候选受体。然而，fz基因的零突变对Wg信号转导几乎没有影响，而fz2基因的缺乏到目前为止阻碍了对其在体内的作用的严格检查。在这里，我们描述了fz2的琥珀突变的分离，该突变在氨基末端胞外区之后截断编码序列，并在遗传学上表现为功能丧失的等位基因。利用这种突变，我们发现Wg信号转导在胚胎和翅膀成像盘中几乎所有缺乏Fz和Fz2活性的细胞中都被取消。我们还表明Fz和Fz2在功能上是多余的：在整个发育过程中，任何一种蛋白质的存在都足以赋予大多数或所有细胞Wg转导活性。这些结果扩展了先前关于Wnt和Frizzled蛋白质之间存在配基-受体关系的证据，并表明Fz和Fz2是果蝇中Wg的主要受体。
Wingless (Wg) protein is a founding member of the Wnt family of secreted proteins which have profound organizing roles in animal development. Two members of the Frizzled (Fz) family of seven-pass transmembrane proteins, Drosophila Fz and Fz2, can bind Wg and are candidate Wg receptors. However, null mutations of the fz gene have little effect on Wg signal transduction and the lack of mutations in the fz2 gene has thus far prevented a rigorous examination of its role in vivo. Here we describe the isolation of an amber mutation of fz2 which truncates the coding sequence just after the amino-terminal extracellular domain and behaves genetically as a loss-of-function allele. Using this mutation, we show that Wg signal transduction is abolished in virtually all cells lacking both Fz and Fz2 activity in embryos as well as in the wing imaginal disc. We also show that Fz and Fz2 are functionally redundant: the presence of either protein is sufficient to confer Wg transducing activity on most or all cells throughout development. These results extend prior evidence of a ligand-receptor relationship between Wnt and Frizzled proteins and suggest that Fz and Fz2 are the primary receptors for Wg in Drosophila.