Hiramoto M, Hiromi Y, Giniger E, Hotta Y
Department of Developmental Genetics, National Institute of Genetics, Graduate University for Advanced Studies, Japan.
Nature. 2000 Aug 24;406(6798):886-9. doi: 10.1038/35022571.
Netrin is a secreted protein that can act as a chemotropic axon guidance cue. Two classes of Netrin receptor, DCC and UNC-5 (refs 6-9), are required for axon guidance and are thought to mediate Netrin signals in growth cones through their cytoplasmic domains. However, in the guidance of Drosophila photoreceptor axons, the DCC orthologue Frazzled is required not in the photoreceptor neurons but instead in their targets, indicating that Frazzled also has a non-cell-autonomous function. Here we show that Frazzled can capture Netrin and 'present' it for recognition by other receptors. Moreover, Frazzled itself is actively localized within the axon through its cytoplasmic domain, and thereby rearranges Netrin protein into a spatial pattern completely different from the pattern of Netrin gene expression. Frazzled-dependent guidance of one pioneer neuron in the central nervous system can be accounted for solely on the basis of this ability of Frazzled to control Netrin distribution, and not by Frazzled signalling. We propose a model of patterning mechanism in which a receptor rearranges secreted ligand molecules, thereby creating positional information for other receptors.
Netrin是一种分泌蛋白，可作为化学趋向性轴突导向因子。轴突导向需要两类Netrin受体，即DCC和UNC-5（参考文献6 - 9），并且认为它们通过其胞质结构域在生长锥中介导Netrin信号。然而，在果蝇感光神经元轴突的导向中，DCC同源物Frazzled并非在感光神经元中发挥作用，而是在其靶标中发挥作用，这表明Frazzled也具有非细胞自主性功能。在此我们表明，Frazzled能够捕获Netrin并将其“呈递”以供其他受体识别。此外，Frazzled自身通过其胞质结构域在轴突内被主动定位，从而将Netrin蛋白重排为一种与Netrin基因表达模式完全不同的空间模式。中枢神经系统中一个先驱神经元的Frazzled依赖性导向完全可以基于Frazzled控制Netrin分布的这种能力来解释，而不是通过Frazzled信号传导。我们提出了一种模式形成机制模型，其中一种受体重排分泌的配体分子，从而为其他受体创建位置信息。
