Nitta Yohei, Sugie Atsushi
Department of Neuroscience of Disease, Center for Transdisciplinary Research, Niigata University, Japan; Brain Research Institute, Niigata University, Japan.
Biochem Biophys Res Commun. 2017 May 20;487(1):116-121. doi: 10.1016/j.bbrc.2017.04.028. Epub 2017 Apr 8.
Precisely controlled axon guidance for complex neuronal wiring is essential for appropriate neuronal function. c-Jun N-terminal kinase (JNK) was found to play a role in axon guidance recently as well as in cell proliferation, protection and apoptosis. In spite of many genetic and molecular studies on these biological processes regulated by JNK, how JNK regulates axon guidance accurately has not been fully explained thus far. To address this question, we use the Drosophila mushroom body (MB) as a model since the α/β axons project in two distinct directions. Here we show that DISCO interacting protein 2 (DIP2) is required for the accurate direction of axonal guidance. DIP2 expression is under the regulation of Basket (Bsk), the Drosophila homologue of JNK. We additionally found that the Bsk/DIP2 pathway is independent from the AP-1 transcriptional factor complex pathway, which is directly activated by Bsk. In conclusion, our findings revealed DIP2 as a novel effector downstream of Bsk modulating the direction of axon projection.
精确控制轴突导向以实现复杂的神经元布线对于适当的神经元功能至关重要。最近发现c-Jun氨基末端激酶（JNK）在轴突导向以及细胞增殖、保护和凋亡中发挥作用。尽管对由JNK调节的这些生物学过程进行了许多遗传和分子研究，但迄今为止，JNK如何精确调节轴突导向尚未得到充分解释。为了解决这个问题，我们使用果蝇蘑菇体（MB）作为模型，因为α/β轴突向两个不同方向投射。在这里，我们表明DISCO相互作用蛋白2（DIP2）是轴突导向精确方向所必需的。DIP2的表达受JNK的果蝇同源物Basket（Bsk）的调控。我们还发现Bsk/DIP2途径独立于由Bsk直接激活的AP-1转录因子复合体途径。总之，我们的发现揭示了DIP2是Bsk下游调节轴突投射方向的一种新型效应物。
