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首页> 外文期刊>Neuron >Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development
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Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development

机译：神经源素2和Slitrk3的分子解剖显示出Gabaergic突触发育的基本框架

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摘要

Summary In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to?synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction?impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in?concert to control synaptogenesis and establish a general framework for GABAergic synapse development. Highlights ? Neuroligin 2 is critical for GABAergic synapse formation in developing neurons ? As neurons mature, GABAergic synaptogenesis requires both Neuroligin 2 and Slitrk3 ? Neuroligin 2 interacts with Slitrk3 to regulate GABAergic synapse development ? The Neuroligin 2-Slitrk3 interaction is important for hippocampal network activity Li et?al. report a hierarchical process mediated by Neuroligin 2 and Slitrk3 for GABAergic synapse development. Neuroligin 2 also interacts with Slitrk3 to regulate GABAergic synaptogenesis. Selective perturbation of this interaction decreases GABAergic synaptic transmission and impairs hippocampal network activities.
机译：发明内容在大脑中，许多类型的中间核在主要神经元中使功能不同的抑制突触。虽然已经鉴定了许多分子在抑制突触开发中起作用，但仍然未知是否存在对不同抑制突触的统一机制。在这里，我们报告了海马抑制突触发育的一般分子机制。在开发神经元时，胃肠杆菌的建立取决于神经源素2（NL2），突触细胞粘附分子（凸轮）。在成熟期间，抑制突触开发需要NL2和SLITRK3（ST3），另一个凸轮。重要的是，NL2和ST3通过其细胞外结构域与纳摩尔亲和力相互作用？协同促进突触开发。 NL2-ST3相互作用的选择性扰动？损害抑制突触开发，随后对海马网络活动的破坏以及增加的癫痫发作性敏感性。我们的调查结果揭示了突触后凸轮凸轮的独特作用？音乐会控制突触突触和建立Gabaergic Synapse开发的一般框架。强调 ？神经罗素素2对于开发神经元的加巴康突突突染形成至关重要？作为神经元成熟，加布曲突突触术需要神经源素2和Slitrk3？神经源素2与Slitrk3相互作用以调节甘草突触发发吗？神经源素2- slitrk3相互作用对于海马网络活动来重要李等。报告由神经罗素蛋白2和Slitrk3介导进行加法缩症突触开发的分层过程。神经罗素蛋白2还与Slitrk3相互作用以调节胃肠杆菌突触生成。这种相互作用的选择性扰动降低了胃肠杆菌突触传递并损害海马网络活动。

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  • 来源
    《Neuron》 |2017年第4期|共19页
  • 作者

    Jun Li; Wenyan Han; Kenneth A. Pelkey; Jingjing Duan; Xia Mao; Ya-Xian Wang; Michael T. Craig; Lijin Dong; Ronald S. Petralia; Chris J. McBain; Wei Lu;

  • 作者单位

    Synapse and Neural Circuit Research Unit National Institute of Neurological Disorders and Stroke;

    Synapse and Neural Circuit Research Unit National Institute of Neurological Disorders and Stroke;

    Program in Developmental Neuroscience Eunice Kennedy-Shriver National Institute of Child Health;

    Synapse and Neural Circuit Research Unit National Institute of Neurological Disorders and Stroke;

    Synapse and Neural Circuit Research Unit National Institute of Neurological Disorders and Stroke;

    Advanced Imaging Core National Institute on Deafness and Other Communication Disorders National;

    Institute of Biomedical and Clinical Sciences University of Exeter Medical School Hatherly;

    Genetic Engineering Core National Eye Institute National Institutes of Health Bethesda MD 20892;

    Advanced Imaging Core National Institute on Deafness and Other Communication Disorders National;

    Program in Developmental Neuroscience Eunice Kennedy-Shriver National Institute of Child Health;

    Synapse and Neural Circuit Research Unit National Institute of Neurological Disorders and Stroke;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

    GABA; GABAergic synapse; development; Neuroligin 2; Slitrk3; cell adhesion molecule; gephyrin; collybistin; seizure; gamma oscillation;

    机译：GABA;Gabaergic Synapse;发育;神经源素2;slitrk3;细胞粘附分子;gephyrin;素粘蛋白;癫痫发作;伽马振荡;

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