Dynamin and Activity Regulate Synaptic Vesicle Recycling in Sympathetic Neurons
Dynamin and Activity Regulate Synaptic Vesicle Recycling in Sympathetic Neurons
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DOI：
10.1074/jbc.m803691200
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发表时间：
2009-01-16
影响因子：
4.8
通讯作者：
Mochida, Sumiko
中科院分区：
文献类型：
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作者：
Lu, Wenbo;Ma, Huan;Mochida, Sumiko
在中枢神经元突触中，神经递质释放期间和释放后，在不同的时间尺度上通过内吞作用对突触小泡进行循环利用，从而支持神经传递。在此，我们通过使用动力蛋白激活抑制剂Dynasore或一种动力蛋白肽（P4，它通过 amphiphysin干扰动力蛋白与网格蛋白包被的连接）急性破坏内吞作用，研究了培养的颈上神经节神经元之间形成的外周神经元突触中突触小泡循环的不同模式的动力学和分子决定因素。当产生成对的动作电位以产生兴奋性突触后电位反应时，应用Dynasore后第二个反应减弱，但应用P4后没有减弱。此外，在一系列动作电位期间，突触传递的分级降低被Dynasore加速，但被P4增强。在可释放小泡完全耗尽后，P4延迟了突触传递的恢复，而Dynasore使恢复限制在10%。在对照神经元中，在低频突触前刺激（0.2Hz）下，突触传递稳定超过1小时，但在低得多的刺激频率下，P4使突触传递逐渐降低，Dynasore使突触传递迅速但不完全阻断。这些结果表明动力蛋白介导的突触小泡循环有两种基本模式，一种是依赖活动的，另一种是不依赖活动的。我们的发现将目前对突触小泡循环的理解扩展到交感神经末梢，并为内吞作用的生理和分子异质性提供了证据，内吞作用是有效补充小泡池从而实现突触可塑性的关键细胞过程。
Neurotransmission in central neuronal synapses is supported by the recycling of synaptic vesicles via endocytosis at different time scales during and after transmitter release. Here, we examine the kinetics and molecular determinants of different modes of synaptic vesicle recycling at a peripheral neuronal synapse formed between superior cervical ganglion neurons in culture, via acute disruption of endocytosis with Dynasore, an inhibitor of dynamin activation, or a dynamin peptide (P4) that perturbs linkage of dynamin to clathrin coats through amphiphysin. When paired action potentials are generated to produce excitatory postsynaptic potential responses, the second response was reduced after application of Dynasore but not P4. In addition, graded reduction in synaptic transmission during a train of action potentials was accelerated by Dynasore but enhanced by P4. After full depletion of releasable vesicles, P4 delayed the recovery of synaptic transmission while Dynasore limited recovery to 10%. In control neurons, synaptic transmission is stable for more than 1 h under low frequency presynaptic stimulation (0.2 Hz), but was reduced gradually by P4 and rapidly but incompletely blocked by Dynasore at a much lower stimulation frequency. These results suggest two essential modes of dynamin-mediated synaptic vesicle recycling, one activity-dependent and the other activity-independent. Our findings extend the current understanding of synaptic vesicle recycling to sympathetic nerve terminals and provide evidence for a physiological and molecular heterogeneity in endocytosis, a key cellular process for efficient replenishment of the vesicle pool, and thus for synaptic plasticity.