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Dynamic organization of synaptic signaling by distinct neurexophilin/alpha neurexin complexes

不同的神经亲和素/α神经素复合物对突触信号传导的动态组织

基本信息

批准号：
316996371
负责人：
Professor Dr. Markus Missler
金额：
--
依托单位：
Institut für Anatomie und Molekulare Neurobiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/316996371?language=en
关键词：
Dynamic organization synaptic signaling distinct

项目摘要

Synapses mediate signaling between neurons through specialized pre- and postsynaptic membrane domains. Since synapses have to form and adapt to stimuli throughout life, their maintenance depends on the coordinated delivery of key molecules. The cell adhesion molecules neurexins (Nrxn) play essential roles in synapses by acting in concert with binding partners. However, the dynamic behavior and targeting of Nrxn-based complexes inside and outside of synaptic interfaces are largely unknown. We have proposed that complex formation with neurexophilins (Nxph), a unique family of neuropeptide-like alphaNrxn-specific ligands, changes the physiological properties of synapses. Preliminary data show that Nxph1 and Nxph3, expressed in distinct subpopulations of neurons, affect synapses differently. Since recent results revealed that complex formation with Nxph1 regulates the surface mobility of alphaNrxn, Nxph1/alphaNrxn and Nxph3/alphaNrxn complexes may modify signaling at and molecular composition of synaptic interfaces in a locally and functionally distinct way. Here we want to compare the molecular properties of these two complexes and use live imaging to investigate their synaptic targeting in transfected primary hippocampal neurons from wild-type and genetically modified mice. To explore how exactly Nxph1/alphaNrxn and Nxph3/alphaNrxn complexes affect synaptic function, we will analyze neurotransmitter release in these cultures. Thus, our project emphasizes a dynamic view of synapses in which specific and local remodelling of their molecular composition may serve to determine important functional properties of subpopulations of terminals.

突触通过专门的突触前和突触后膜结构域介导神经元之间的信号传导。由于突触必须在整个生命过程中形成并适应刺激，因此它们的维持取决于关键分子的协调传递。细胞粘附分子neurexins（Nrxn）通过与结合伴侣协同作用而在突触中发挥重要作用。然而，基于Nrxn的复合物在突触界面内外的动态行为和靶向在很大程度上是未知的。我们已经提出，复合物形成neurexophilins（Nxph），一个独特的家庭的神经肽样alphaNrxn特异性配体，改变突触的生理特性。初步数据表明，Nxph 1和Nxph 3，在不同的神经元亚群中表达，影响突触不同。由于最近的研究结果表明，与Nxph 1的复合物形成调节的表面流动性的alphaNrxn，Nxph 1/alphaNrxn和Nxph 3/alphaNrxn复合物可以修改信号和分子组成的突触接口在一个本地和功能上不同的方式。在这里，我们想比较这两种复合物的分子特性，并使用实时成像来研究它们在野生型和转基因小鼠的转染原代海马神经元中的突触靶向。为了探索Nxph 1/alphaNrxn和Nxph 3/alphaNrxn复合物如何影响突触功能，我们将分析这些培养物中的神经递质释放。因此，我们的项目强调突触的动态视图，其中特定的和局部的分子组成的重塑可能有助于确定终端的亚群的重要功能特性。