Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo.
Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo.
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发表时间：
2000-02
期刊：
影响因子：
4.6
通讯作者：
Q. Sun;S. Bahri;Aloisia Schmid;William Chia;Kai Zinn
中科院分区：
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作者：
Q. Sun;S. Bahri;Aloisia Schmid;William Chia;Kai Zinn
神经受体连接蛋白酪氨酸磷酸酶（RPTPs）是果蝇运动神经元和感光细胞生长锥所必需的。然而，这些磷酸酶并没有参与生长锥对特定引导信号的反应，因此尚不清楚轴突寻路的哪些方面是由它们的活性控制的。三种RPTP，称为DLAR，DPTP 69 D和DPTP 99 A，迄今已被遗传表征。在这里，我们报告的第四个神经RPTP，DPTP 10 D突变的分离。双突变表型的分析表明，DPTP 10 D和DPTP 69 D是必要的排斥生长锥从中线的胚胎中枢神经系统。排斥被认为是由分泌蛋白Slit（其由中线胶质细胞表达）与生长锥上的Roundabout（Robo）受体结合而触发的。Robo排斥被Commissueless（Comm）蛋白下调，允许轴突穿过中线。在这里，我们表明，Rptp突变的遗传相互作用与机器人，狭缝和通信。这些相互作用的性质表明，DPTP 10 D和DPTP 69 D的狭缝/回旋排斥信号的正调节。我们还表明，消除所有四个神经RPTPs转换成连合，跨越中线的最noncrossing纵向通路，表明酪氨酸磷酸化控制的方式，生长锥响应中线信号。
Neural receptor-linked protein tyrosine phosphatases (RPTPs) are required for guidance of motoneuron and photoreceptor growth cones in Drosophila. These phosphatases have not been implicated in growth cone responses to specific guidance cues, however, so it is unknown which aspects of axonal pathfinding are controlled by their activities. Three RPTPs, known as DLAR, DPTP69D, and DPTP99A, have been genetically characterized thus far. Here we report the isolation of mutations in the fourth neural RPTP, DPTP10D. The analysis of double mutant phenotypes shows that DPTP10D and DPTP69D are necessary for repulsion of growth cones from the midline of the embryonic central nervous system. Repulsion is thought to be triggered by binding of the secreted protein Slit, which is expressed by midline glia, to Roundabout (Robo) receptors on growth cones. Robo repulsion is downregulated by the Commissureless (Comm) protein, allowing axons to cross the midline. Here we show that the Rptp mutations genetically interact with robo, slit and comm. The nature of these interactions suggests that DPTP10D and DPTP69D are positive regulators of Slit/Roundabout repulsive signaling. We also show that elimination of all four neural RPTPs converts most noncrossing longitudinal pathways into commissures that cross the midline, indicating that tyrosine phosphorylation controls the manner in which growth cones respond to midline signals.