Levitan Edwin S
Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Mol Neurobiol. 2008 Feb;37(1):39-43. doi: 10.1007/s12035-008-8014-3. Epub 2008 Apr 30.
The hypothesis that release of classical neurotransmitters and neuropeptides is facilitated by increasing the mobility of small synaptic vesicles (SSVs) and dense core vesicles (DCVs) could not be tested until the advent of methods for visualizing these secretory vesicles in living nerve terminals. In fact, fluorescence imaging studies have only since 2005 established that activity increases secretory vesicle mobility in motoneuron terminals and chromaffin cells. Mobilization of DCVs and SSVs appears to be due to liberation of hindered vesicles to promote quicker diffusion. However, F-actin and synapsin, which have been featured in mobilization models, are not required for activity-dependent increases in the mobility of DCVs or SSVs. Most recently, the signaling required for sustained mobilization has been identified for Drosophila motoneuron DCVs and shown to increase synaptic transmission. Specifically, presynaptic endoplasmic reticulum ryanodine receptor-mediated Ca2+ release activates Ca2+/calmodulin-dependent kinase II to mobilize DCVs and induce post-tetanic potentiation (PTP) of neuropeptide release in the Drosophila neuromuscular junction. The shared signaling for increasing vesicle mobility and PTP links vesicle mobilization and synaptic plasticity.
在能够对活神经末梢中的这些分泌囊泡进行可视化的方法出现之前，经典神经递质和神经肽的释放是通过增加小突触囊泡（SSV）和致密核心囊泡（DCV）的流动性来促进的这一假说无法得到验证。事实上，荧光成像研究直到2005年才证实，活动会增加运动神经元末梢和嗜铬细胞中分泌囊泡的流动性。DCV和SSV的动员似乎是由于受阻囊泡的释放以促进更快的扩散。然而，在动员模型中起作用的F-肌动蛋白和突触结合蛋白，对于DCV或SSV流动性的活动依赖性增加并非必需。最近，已确定果蝇运动神经元DCV持续动员所需的信号传导，并表明其可增加突触传递。具体而言，突触前内质网ryanodine受体介导的Ca2+释放激活Ca2+/钙调蛋白依赖性激酶II，以动员DCV并诱导果蝇神经肌肉接头处神经肽释放的强直后增强（PTP）。增加囊泡流动性和PTP的共同信号传导将囊泡动员与突触可塑性联系起来。
