Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, 1081 HV Amsterdam, Netherlands.
J Cell Biol. 2012 Dec 10;199(6):883-91. doi: 10.1083/jcb.201208024.
Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.
神经元致密核心囊泡 (DCVs) 包含多种对大脑发育和功能至关重要的货物，但控制其释放的机制在很大程度上尚不清楚。我们在海马神经元中以单个囊泡分辨率定量了活性依赖性 DCV 释放。DCVs 优先在突触末端融合。DCVs 也可以在突触外位点融合，但仅在长时间刺激后。在 munc13-1/2 缺失突变神经元中，突触 DCV 释放减少但未完全消除，突触偏好丧失。剩余的融合需要长时间刺激，类似于野生型神经元中的突触外融合。相反，Munc13-1 过表达 (M13OE) 促进了突触外 DCV 释放，也不需要长时间刺激。因此，Munc13-1/2 促进 DCV 融合，但与突触囊泡不同，对于 DCV 释放不是必需的，并且 M13OE 足以有效地进行突触外 DCV 释放。
