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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基于 Neurexin 和 Neuroligin 的粘附复合物可独立于突触活动驱动轴突树枝化生长。

DOI:
10.7554/elife.31659
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发表时间:
2018-03-05
期刊:
影响因子:
7.7
通讯作者:
Williams DW
Williams DW
中科院分区:
生物学1区
文献类型:
--
作者:
Constance WD;Mukherjee A;Fisher YE;Pop S;Blanc E;Toyama Y;Williams DW

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构建正确大小和形状的分支是神经网络功能的基础。脊椎动物大脑的活体成像强烈表明,新生突触对发育过程中的分支生长至关重要。这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arborisations生活,在体内变态过程中的发展。在生长的树枝状结构中,我们看到突触前蛋白的分支动力学和定位与鱼类/青蛙中描述的“向突触生长”非常相似。这些突触前蛋白的积累似乎不是突触前释放位点,也不与神经递质受体配对。敲除诱发或自发的神经传递不影响乔木生长。相反,我们发现轴突分支的生长是由Neurexin和Neuroligin的动态局部定位所调控的。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稳定性。
Building arborisations of the right size and shape is fundamental for neural network function. Live imaging in vertebrate brains strongly suggests that nascent synapses are critical for branch growth during development. The molecular mechanisms underlying this are largely unknown. Here we present a novel system in Drosophila for studying the development of complex arborisations live, in vivo during metamorphosis. In growing arborisations we see branch dynamics and localisations of presynaptic proteins very similar to the ‘synaptotropic growth’ described in fish/frogs. These accumulations of presynaptic proteins do not appear to be presynaptic release sites and are not paired with neurotransmitter receptors. Knockdowns of either evoked or spontaneous neurotransmission do not impact arbor growth. Instead, we find that axonal branch growth is regulated by dynamic, focal localisations of Neurexin and Neuroligin. These adhesion complexes provide stability for filopodia by a ‘stick-and-grow’ based mechanism wholly independent of synaptic activity.