Active Zone Material-Directed Orientation, Docking, and Fusion of Dense Core Vesicles Alongside Synaptic Vesicles at Neuromuscular Junctions.

Active Zone Material-Directed Orientation, Docking, and Fusion of Dense Core Vesicles Alongside Synaptic Vesicles at Neuromuscular Junctions.
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DOI:
10.3389/fnana.2018.00072
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发表时间:
2018
影响因子:
2.9
通讯作者:
McMahan UJ
McMahan UJ
中科院分区:
医学3区
文献类型:
--
作者:
Jung JH;Szule JA;Stouder K;Marshall RM;McMahan UJ

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活性区物质是化学突触突触前膜活性区共有的细胞器。青蛙神经肌肉连接处活跃区的电子断层扫描提供了证据,表明活跃区的物质指导突触囊泡(SVs)在该突触的突触前膜上对接。某些活性区物质大分子连接到未对接的sv膜中典型排列的大分子,稳定地将囊泡膜的预定融合区域定向到突触前膜,同时将两个膜结合在一起。冲激触发的囊泡膜-突触前膜融合需要囊泡对接,从而将囊泡的神经递质释放到突触间隙中。与其他突触一样,青蛙神经肌肉连接处的轴突末端除了含有sv外,还含有更大、更少的囊泡,并且在电子显微镜下观察时,具有独特的电子密集核心。神经肌肉连接处致密的核心囊泡可能含有肽,这些肽被释放到突触间隙中,以调节突触冲动传递所必需的细胞装置的形成、维持和行为。我们通过电子断层扫描显示,青蛙神经肌肉连接的轴突末端在静止状态和重复脉冲传递过程中固定,密集的核心囊泡选择性地与突触前膜对接并融合在活跃区,活跃区物质与密集的核心囊泡连接在一起,经历这些过程,与连接到SVs的方式相同。我们得出结论,未对接的致密核心囊泡具有预定的融合域,未对接的sv也是如此,活性区物质通过类似的大分子相互作用,在突触前膜的活性区指导这些不同囊泡类型的定向对接和融合。
Active zone material is an organelle that is common to active zones along the presynaptic membrane of chemical synapses. Electron tomography on active zones at frog neuromuscular junctions has provided evidence that active zone material directs the docking of synaptic vesicles (SVs) on the presynaptic membrane at this synapse. Certain active zone material macromolecules connect to stereotypically arranged macromolecules in the membrane of undocked SVs, stably orienting a predetermined fusion domain of the vesicle membrane toward the presynaptic membrane while bringing and holding the two membranes together. Docking of the vesicles is required for the impulse-triggered vesicle membrane-presynaptic membrane fusion that releases the vesicles’ neurotransmitter into the synaptic cleft. As at other synapses, axon terminals at frog neuromuscular junctions contain, in addition to SVs, vesicles that are larger, are much less frequent and, when viewed by electron microscopy, have a distinctive electron dense core. Dense core vesicles at neuromuscular junctions are likely to contain peptides that are released into the synaptic cleft to regulate formation, maintenance and behavior of cellular apparatus essential for synaptic impulse transmission. We show by electron tomography on axon terminals of frog neuromuscular junctions fixed at rest and during repetitive impulse transmission that dense core vesicles selectively dock on and fuse with the presynaptic membrane alongside SVs at active zones, and that active zone material connects to the dense core vesicles undergoing these processes in the same way it connects to SVs. We conclude that undocked dense core vesicles have a predetermined fusion domain, as do undocked SVs, and that active zone material directs oriented docking and fusion of these different vesicle types at active zones of the presynaptic membrane by similar macromolecular interactions.
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