Munc13 controls the location and efficiency of dense-core vesicle release in neurons.
Munc13 controls the location and efficiency of dense-core vesicle release in neurons.
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DOI：
10.1083/jcb.201208024
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发表时间：
2012-12-10
期刊：
影响因子：
--
通讯作者：
Toonen RF
中科院分区：
文献类型：
--
作者：
van de Bospoort R;Farina M;Schmitz SK;de Jong A;de Wit H;Verhage M;Toonen RF
尽管 Munc13-1 和 Munc13-2 促进致密核心囊泡融合，但它们不是 DCV 释放所必需的，这与它们在突触囊泡胞吐作用中的重要作用相反。神经元致密核心囊泡（DCV）含有对大脑发育和功能至关重要的多种物质，但控制其释放的机制很大程度上未知。我们以单囊泡分辨率量化了海马神经元中活动依赖性 DCV 释放。 DCV 优先在突触末端融合。 DCV 也在突触外部位融合，但仅在长时间刺激后才发生。在munc13-1/2缺失突变神经元中，突触DCV释放减少但并未消除，并且突触偏好消失。剩余的融合需要长时间的刺激，类似于野生型神经元的突触外融合。相反，Munc13-1 过表达（M13OE）促进突触外 DCV 释放，而且无需长时间刺激。因此，Munc13-1/2 促进 DCV 融合，但与突触小泡不同，Munc13-1/2 对于 DCV 释放不是必需的，并且 M13OE 足以在突触外产生有效的 DCV 释放。
Although Munc13-1 and Munc13-2 facilitate dense-core vesicle fusion, they are not required for DCV release, in contrast to their essential role in synaptic vesicle exocytosis. 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.
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