Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling
Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling
复制标题
DOI：
10.1016/j.neuron.2008.01.026
复制
发表时间：
2008-03-13
期刊：
影响因子：
16.2
通讯作者：
Budnik, Vivian
中科院分区：
文献类型：
--
作者：
Ataman, Bulent;Ashley, James;Budnik, Vivian
突触结构的活动依赖性修饰在突触发育和可塑性中起着关键作用，但涉及的信号转导机制知之甚少。我们证明，果蝇神经肌肉接头的突触结构和功能的快速变化，在响应模式的刺激。这些变化，这取决于转录和翻译，包括形成运动的突触前丝状伪足，阐述未分化的静脉曲张，并增强自发释放频率。实验表明，双向Wnt/Wg信号通路的基础这些变化。诱发活动诱导Wnt 1/Wg从突触终扣释放，其刺激突触后DFz 2核输入通路以及涉及GSK-3 β/Shaggy的突触前通路。我们的研究结果表明，双向Wg信号传导在突触活动的下游起作用，以诱导突触结构和功能的改变。我们建议，激活的突触后Wg通路的突触后装置的组装是必需的，而激活的突触前Wg通路调节细胞骨架动力学。
Activity-dependent modifications in synapse structure play a key role in synaptic development and plasticity, but the signaling mechanisms involved are poorly understood. We demonstrate that glutamatergic Drosophila neuromuscular junctions undergo rapid changes in synaptic structure and function in response to patterned stimulation. These changes, which depend on transcription and translation, include formation of motile presynaptic filopodia, elaboration of undifferentiated varicosities, and potentiation of spontaneous release frequency. Experiments indicate that a bidirectional Wnt/Wg signaling pathway underlies these changes. Evoked activity induces Wnt1/Wg release from synaptic boutons, which stimulates both a postsynaptic DFz2 nuclear import pathway as well as a presynaptic pathway involving GSK-3 beta/Shaggy. Our findings suggest that bidirectional Wg signaling operates downstream of synaptic activity to induce modifications in synaptic structure and function. We propose that activation of the postsynaptic Wg pathway is required for the assembly of the postsynaptic apparatus, while activation of the presynaptic Wg pathway regulates cytoskeletal dynamics.