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首页> 外文期刊>PLoS One >Terminal Axonal Arborization and Synaptic Bouton Formation Critically Rely on Abp1 and the Arp2/3 Complex
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Terminal Axonal Arborization and Synaptic Bouton Formation Critically Rely on Abp1 and the Arp2/3 Complex

机译:终末轴突乔化和突触Bouton形成严重依赖于Abp1和Arp2 / 3复杂。

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Neuronal network formation depends on properly timed and localized generation of presynaptic as well as postsynaptic structures. Although of utmost importance for understanding development and plasticity of the nervous system and neurodegenerative diseases, the molecular mechanisms that ensure the fine-control needed for coordinated establishment of pre- and postsynapses are still largely unknown. We show that the F-actin-binding protein Abp1 is prominently expressed in the Drosophila nervous system and reveal that Abp1 is an important regulator in shaping glutamatergic neuromuscular junctions (NMJs) of flies. STED microscopy shows that Abp1 accumulations can be found in close proximity of synaptic vesicles and at the cell cortex in nerve terminals. Abp1 knock-out larvae have locomotion defects and underdeveloped NMJs that are characterized by a reduced number of both type Ib synaptic boutons and branches of motornerve terminals. Abp1 is able to indirectly trigger Arp2/3 complex-mediated actin nucleation and interacts with both WASP and Scar. Consistently, Arp2 and Arp3 loss-of-function also resulted in impairments of bouton formation and arborization at NMJs, i.e. fully phenocopied abp1 knock-out. Interestingly, neuron- and muscle-specific rescue experiments revealed that synaptic bouton formation critically depends on presynaptic Abp1, whereas the NMJ branching defects can be compensated for by restoring Abp1 functions at either side. In line with this presynaptic importance of Abp1, also presynaptic Arp2 and Arp3 are crucial for the formation of type Ib synaptic boutons. Interestingly, presynaptic Abp1 functions in NMJ formation were fully dependent on the Arp2/3 complex, as revealed by suppression of Abp1-induced synaptic bouton formation and branching of axon terminals upon presynaptic Arp2 RNAi. These data reveal that Abp1 and Arp2/3 complex-mediated actin cytoskeletal dynamics drive both synaptic bouton formation and NMJ branching. Our data furthermore shed light on an intense bidirectional functional crosstalk between pre- and postsynapses during the development of synaptic contacts.
机译:神经元网络的形成取决于突触前和突触后结构的适当定时和局部生成。尽管对于理解神经系统和神经退行性疾病的发展和可塑性至关重要,但是确保协调突触前和突触建立所需的精细控制的分子机制仍然未知。我们显示F-肌动蛋白结合蛋白Abp1在果蝇神经系统中突出表达,并揭示Abp1是塑造苍蝇谷氨酸能神经肌肉接头(NMJs)的重要调节器。 STED显微镜显示,Abp1积累可在突触小泡附近和神经末梢的细胞皮层中发现。 Abp1敲除幼虫具有运动缺陷和不发达的NMJ,其特征是Ib型突触钮扣和运动神经末梢分支的数量减少。 Abp1能够间接触发Arp2 / 3复合物介导的肌动蛋白成核,并与WASP和Scar相互作用。一致地,Arp2和Arp3的功能丧失也导致NMJ的钮扣形成和乔木化受损,即完全表型的abp1敲除。有趣的是,特定于神经元和肌肉的抢救实验表明,突触的bouton形成关键取决于突触前的Abp1,而NMJ分支缺陷可以通过在任一侧恢复Abp1的功能来弥补。与此突触前Abp1的重要性相一致,突触前Arp2和Arp3对于Ib型突触钮扣的形成也至关重要。有趣的是,NMJ形成中的突触前Abp1功能完全依赖于Arp2 / 3复合物,如通过抑制Abp1诱导的突触钮扣形成和突触前Arp2 RNAi轴突末端分支所揭示的那样。这些数据表明,Abp1和Arp2 / 3复合物介导的肌动蛋白细胞骨架动力学既驱动突触钮扣形成,又驱动NMJ分支。我们的数据进一步揭示了突触接触发展过程中突触前和突触之间强烈的双向功能性串扰。

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