cGMP-Dependent Protein Kinase Encoded by foraging Regulates Motor Axon Guidance in Drosophila by Suppressing Lola Function
cGMP-Dependent Protein Kinase Encoded by foraging Regulates Motor Axon Guidance in Drosophila by Suppressing Lola Function
复制标题
觅食编码的 cGMP 依赖性蛋白激酶通过抑制 Lola 功能调节果蝇运动轴突引导
DOI：
10.1523/jneurosci.3726-15.2016
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发表时间：
2016-04-20
影响因子：
5.3
通讯作者：
Liu, Li
中科院分区：
文献类型：
--
作者：
Peng, Qionglin;Wang, Yijin;Liu, Li
对发育中的轴突进行正确的路径寻找和目标识别是需要多种指导因素的精细调控过程。在这些因素中，第二信使cAMP和cGMP被认为通过不同的细胞内信号通路参与建立轴突生长的指导信号。然而，cGMP依赖的蛋白激酶(PKG)是否以及如何调节轴突导向仍然知之甚少。在这里，我们证明了果蝇胚胎节间神经b(ISNb)的运动轴突在缺乏觅食(For)的情况下，在轴突发育过程中显示出靶向性缺陷。For是一种编码PKG的基因。在体内的表达表明，PKG在胚胎晚期存在于腹神经编码中，支持其在胚胎轴突引导中的功能。机制研究表明，转录因子纵向缺失(LOLA)与FOR在遗传上相互作用。PKG通过C端含锌指结构域与Lolat异构体发生物理结合。在S2细胞中，PKG的过表达导致LOLAT的胞浆滞留，提示PKG在介导LOLA的核质转运中发挥作用。总之，这些发现揭示了PKG通过将LOLA隔离在细胞质中来调节神经元连通性建立的新功能。意义陈述轴突寻路和目标识别是形成特定神经元连接的重要过程，依赖于多种引导因子的精确协调部署。本文揭示了cGMP依赖的蛋白激酶(PKG)在调节果蝇发育中轴突的寻路和靶向中的作用。此外，我们的研究表明，PKG调节转录因子Lolat的胞质-核转运，提示PKG在指导运动轴突导引方面存在机制。这些发现突出了PKG通过抑制转录因子在轴突引导中的新功能。
Correct pathfinding and target recognition of a developing axon are exquisitely regulated processes that require multiple guidance factors. Among these factors, the second messengers, cAMP and cGMP, are known to be involved in establishing the guidance cues for axon growth through different intracellular signaling pathways. However, whether and how cGMP-dependent protein kinase (PKG) regulates axon guidance remains poorly understood. Here, we show that the motor axons of intersegmental nerve b (ISNb) in the Drosophila embryo display targeting defects during axon development in the absence of foraging (for), a gene encoding PKG. In vivo tag expression revealed PKG to be present in the ventral nerve code at late embryonic stages, supporting its function in embryonic axon guidance. Mechanistic studies showed that the transcription factor longitudinal lacking (lola) genetically interacts with for. PKG physically associates with the LolaT isoform via the C-terminal zinc-finger-containing domain. Overexpression of PKG leads to the cytoplasmic retention of LolaT in S2 cells, suggesting a role for PKG in mediating the nucleocytoplasmic trafficking of Lola. Together, these findings reveal a novel function of PKG in regulating the establishment of neuronal connectivity by sequestering Lola in the cytoplasm. SIGNIFICANCE STATEMENT Axon pathfinding and target recognition are important processes in the formation of specific neuronal connectivity, which rely upon precise coordinated deployment of multiple guidance factors. This paper reveals the role of cGMP-dependent protein kinase (PKG) in regulating the pathfinding and targeting of the developing axons in Drosophila. Moreover, our study indicates that PKG regulates the cytoplasmic-nuclear trafficking of the transcription factor LolaT, suggesting a mechanism of PKG in directing motor axon guidance. These findings highlight a new function of PKG in axon guidance by suppressing a transcription factor.