Neurexin and Neuroligin-based adhesion complexes drive axonal arborisation growth independent of synaptic activity
Neurexin and Neuroligin-based adhesion complexes drive axonal arborisation growth independent of synaptic activity
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DOI：
10.1101/182808
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发表时间：
2017-08
期刊：
影响因子：
7.7
通讯作者：
William D Constance;A. Mukherjee;Yvette E. Fisher;S. Pop;E. Blanc;Y. Toyama;Darren W. Williams
中科院分区：
文献类型：
--
作者：
William D Constance;A. Mukherjee;Yvette E. Fisher;S. Pop;E. Blanc;Y. Toyama;Darren W. Williams
构建正确大小和形状的分支是神经网络功能的基础。脊椎动物脑的活体成像研究强烈表明，在轴突和树突分支发育过程中，新生突触对分支生长至关重要。这种“突触”事件背后的分子机制在很大程度上是未知的。在这里，我们提出了一个新的系统，在果蝇研究复杂的轴突arborisations生活，在体内变态过程中的发展。在这些生长的轴突分支中，我们看到突触前成分的点状定位和分支动力学之间的关系，这与鱼类和青蛙中描述的向突触生长非常相似。然而，这些突触前成分似乎并不代表功能性突触前释放位点，也不与神经递质受体簇配对。诱发和自发神经传递的药理学和遗传学敲低不影响这些神经元的生长。相反，我们发现轴突分支的生长是由突触粘附蛋白Neurexin和Neuroligin的动态局部定位调节的。这些粘附复合物通过完全独立于突触活性的基于“粘附和生长”的机制为丝状伪足提供选择性稳定性。
Building arborisations of the right size and shape is fundamental for neural network function. Live imaging studies in vertebrate brains strongly suggest that nascent synapses are critical for branch growth during the development of axonal and dendritic arborisations. The molecular mechanisms underlying such ‘synaptotropic’ events are largely unknown. Here we present a novel system in Drosophila for studying the development of complex axonal arborisations live, in vivo during metamorphosis. In these growing axonal arborisations we see a relationship between the punctate localisations of presynaptic components and branch dynamics that is very similar to synaptotropic growth described in fish and frogs. These presynaptic components however do not appear to represent functional presynaptic release sites and are not paired with clusters of neurotransmitter receptors. Pharmacological and genetic knockdowns of evoked and spontaneous neurotransmission do not impact the outgrowth of these neurons. Instead, we find that axonal branch growth is regulated by the dynamic focal localisations of synaptic adhesion proteins Neurexin and Neuroligin. These adhesion complexes provide selective stability for filopodia by a ‘stick and grow’-based mechanism wholly independent of synaptic activity.