Rapid Assembly of Presynaptic Materials behind the Growth Cone in Dopaminergic Neurons Is Mediated by Precise Regulation of Axonal Transport.
Rapid Assembly of Presynaptic Materials behind the Growth Cone in Dopaminergic Neurons Is Mediated by Precise Regulation of Axonal Transport.
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DOI：
10.1016/j.celrep.2018.07.096
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发表时间：
2018-09-04
期刊：
影响因子：
8.8
通讯作者：
Shen K
中科院分区：
文献类型：
--
作者：
Lipton DM;Maeder CI;Shen K
神经回路的正确组装取决于突触发生的过程，或伴侣神经元之间突触的形成。利用秀丽隐杆线虫的多巴胺能PDE神经元，我们开发了一个体内系统来研究在一个延伸的生长锥后面的突触前特化形成的最早步骤。我们发现突触前物质在短短几分钟内结合成点，突触囊泡（SV）和活性区（AZ）蛋白几乎同时到达突触形成的新生位点。我们发现UNC-104/Kinesin-3的精确调控决定了SV蛋白沿轴突的分布。然而，AZ蛋白在经过点的定位在很大程度上独立于主要的轴突运动蛋白：UNC-104/Kinesin-3和UNC-116/ Kinesin-1。此外，AZ蛋白在募集和捆绑SV前体（svp）中起着至关重要的作用。Lipton等人探索了突触在体内形成的初始步骤。他们发现主要突触前物质的聚集发生得非常快（<5分钟）。突触囊泡前体和活性区蛋白在发育点同时积累。在发育过程中，驱动蛋白-3激活状态的精确调控强烈影响着沿轴突的囊泡定位。
The proper assembly of neural circuits depends on the process of synaptogenesis, or the formation of synapses between partner neurons. Using the dopaminergic PDE neurons in C. elegans, we developed an in vivo system to study the earliest steps of the formation of en passant presynaptic specializations behind an extending growth cone. We find that presynaptic materials coalesce into puncta in as little as a few minutes and that both synaptic vesicle (SV) and active zone (AZ) proteins arrive nearly simultaneously at the nascent sites of synapse formation. We show that precise regulation of UNC-104/Kinesin-3 determines the distribution of SV proteins along the axon. The localization of AZ proteins to en passant puncta, however, is largely independent of the major axonal kinesins: UNC-104/Kinesin-3 and UNC-116/ Kinesin-1. Moreover, AZ proteins play a crucial role in recruiting and tethering SV precursors (SVPs). Lipton et al. explore the initial steps of synapse formation in vivo. They find that clustering of major presynaptic material occurs extremely rapidly (<5 min). Both synaptic vesicle precursors and active zone proteins accumulate simultaneously at developing puncta. Precise regulation of the Kinesin-3 activation state strongly influences the positioning of vesicles along the axon during development.
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