Carihann Dominicci-Cotto, Mariam Vazquez, Bruno Marie
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引用次数: 0
摘要
从苍蝇到人类,Wingless(Wg)/Wnt 信号分子对神经系统的稳定性和可塑性都至关重要。果蝇神经肌肉接头(NMJ)已被证明是一个有用的系统,可用于破译 Wg 在指导活动依赖性突触可塑性(ADSP)中的作用。在这里,我们发现非规范的平面细胞极性(PCP)通路是控制运动神经元突触可塑性的 Wg 信号系统的重要组成部分。我们提出了干扰 PCP 通路导致 ADSP 受扰的证据。我们首先证明了PCP特异性等位基因disheveled(dsh)会影响ADSP过程中产生的新生突触结构。然后,我们表明,PCP 通路中 Dsh 下游的 Rho GTPases 也参与调节反复刺激后发生的形态变化。最后,我们证明 Jun 激酶对这一现象至关重要,而我们没有发现转录因子复合体 AP1(Jun/Fos)参与其中的迹象。这项工作表明神经元 PCP 信号通路参与支持 ADSP。由于我们发现 AP1 突变体可以充分执行 ADSP,因此我们推测,在 Wg 激活后,Rho GTPases 和 Jun 激酶在突触局部参与了细胞骨架动力学的指示,导致 ADSP 期间出现形态变化。
The Wingless planar cell polarity pathway is essential for optimal activity-dependent synaptic plasticity.
From fly to man, the Wingless (Wg)/Wnt signaling molecule is essential for both the stability and plasticity of the nervous system. The Drosophila neuromuscular junction (NMJ) has proven to be a useful system for deciphering the role of Wg in directing activity-dependent synaptic plasticity (ADSP), which, in the motoneuron, has been shown to be dependent on both the canonical and the noncanonical calcium Wg pathways. Here we show that the noncanonical planar cell polarity (PCP) pathway is an essential component of the Wg signaling system controlling plasticity at the motoneuron synapse. We present evidence that disturbing the PCP pathway leads to a perturbation in ADSP. We first show that a PCP-specific allele of disheveled (dsh) affects the de novo synaptic structures produced during ADSP. We then show that the Rho GTPases downstream of Dsh in the PCP pathway are also involved in regulating the morphological changes that take place after repeated stimulation. Finally, we show that Jun kinase is essential for this phenomenon, whereas we found no indication of the involvement of the transcription factor complex AP1 (Jun/Fos). This work shows the involvement of the neuronal PCP signaling pathway in supporting ADSP. Because we find that AP1 mutants can perform ADSP adequately, we hypothesize that, upon Wg activation, the Rho GTPases and Jun kinase are involved locally at the synapse, in instructing cytoskeletal dynamics responsible for the appearance of the morphological changes occurring during ADSP.