The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor frazzled in Drosophila
The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor frazzled in Drosophila
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DOI：
10.1242/dev.01736
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发表时间：
2005-04-01
期刊：
影响因子：
4.6
通讯作者：
Seeger, MA
中科院分区：
文献类型：
--
作者：
Forsthoefel, DJ;Liebl, EC;Seeger, MA
诱人的Netrin受体脆化(Fra)、信号分子Abelson酪氨酸激酶(Abl)、鸟嘌呤核苷酸交换因子Trio和Abl底物使能(Ena)都调节果蝇胚胎CNS中线的轴突路径。我们检测到FrA和这些效应器分子之间的遗传和/或物理相互作用，这表明它们协同行动，引导轴突穿过中线。An和trio的突变主要增强了fra和netrin突变的CNS表型，而fra；abl和fra；trio双突变在大多数连合中表现出显著的轴突丢失。相反，ena的杂合性降低了CNS表型inra，netrin和trio，abl突变体的严重程度。与这些分子作为Fra信号效应器的体内作用一致，Abl、Trio或Ena的杂合性减少了表达嵌合Robo-Fra受体的胚胎中不适当地穿过中线的轴突数量。在GST-Pull试验和免疫共沉淀实验中，FRA与Abl和Trio发生物理作用。此外，在S2细胞中，当Abl水平增加时，Trio和Fra的酪氨酸磷酸化水平也增加。综上所述，这些数据表明Abl、Trio、Ena和Fra被整合到一个复杂的信号网络中，该网络调节中枢神经系统中线的轴突引导。
The attractive Netrin receptor Frazzled (Fra), and the signaling molecules Abelson tyrosine kinase (Abl), the guanine nucleotide-exchange factor Trio, and the Abl substrate Enabled (Ena), all regulate axon pathfinding at the Drosophila embryonic CNS midline. We detect genetic and/or physical interactions between Fra and these effector molecules that suggest that they act in concert to guide axons across the midline. Mutations in AN and trio dominantly enhance fra and Netrin mutant CNS phenotypes, and fra;Abl and fra;trio double mutants display a dramatic loss of axons in a majority of commissures. Conversely, heterozygosity for ena reduces the severity of the CNS phenotype infra, Netrin and trio,Abl mutants. Consistent with an in vivo role for these molecules as effectors of Fra signaling, heterozygosity for Abl, trio or ena reduces the number of axons that inappropriately cross the midline in embryos expressing the chimeric Robo-Fra receptor. Fra interacts physically with Abl and Trio in GST-pulldown assays and in co-immunoprecipitation experiments. In addition, tyrosine phosphorylation of Trio and Fra is elevated in S2 cells when Abl levels are increased. Together, these data suggest that Abl, Trio, Ena and Fra are integrated into a complex signaling network that regulates axon guidance at the CNS midline.