Synaptic transmission requires a stable pool of release-ready (primed) vesicles. Here we show that two molecules involved in SNARE-complex assembly, Munc13-1 and Munc18-1, together stabilize release-ready vesicles by preventing de-priming. Replacing neuronal Munc18-1 by a non-neuronal isoform Munc18-2 (Munc18-1/2SWAP) supports activity-dependent priming, but primed vesicles fall back into a non-releasable state (de-prime) within seconds. Munc13-1 deficiency produces a similar defect. Inhibitors of N-ethylmaleimide sensitive factor (NSF), N-ethylmaleimide (NEM) or interfering peptides, prevent de-priming in munc18-1/2SWAP or munc13-1 null synapses, but not in CAPS-1/2 null, another priming-deficient mutant. NEM rescues synaptic transmission in munc13-1 null and munc18-1/2SWAP synapses, in acute munc13-1 null slices and even partially in munc13-1/2 double null synapses. Together these data indicate that Munc13-1 and Munc18-1, but not CAPS-1/2, stabilize primed synaptic vesicles by preventing NSF-dependent de-priming.

中文翻译：

---

Munc13-1和Munc18-1一起防止NSF依赖的突触小泡的引发。

突触传递需要稳定的准备释放（预备）囊泡池。在这里，我们显示参与SNARE复杂装配的两个分子Munc13-1和Munc18-1通过防止去引发而共同稳定了可释放的囊泡。用非神经元同种型Munc18-2（Munc18-1 / 2SWAP）取代神经元Munc18-1支持依赖于活动的启动，但启动后的囊泡会在几秒钟内退回到不可释放状态（去启动）。Munc13-1缺陷会产生类似的缺陷。N-乙基马来酰亚胺敏感因子（NSF），N-乙基马来酰亚胺（NEM）或干扰肽的抑制剂可防止在munc18-1 / 2SWAP或munc13-1无效突触中消除引发，但在CAPS-1 / 2无效突触中不能防止引发。 -缺陷突变体。NEM抢救了munc13-1 null和munc18-1 / 2SWAP突触中的突触传递，在急性munc13-1无效切片中，甚至部分在munc13-1 / 2双重无效突触中。这些数据一起表明，Munc13-1和Munc18-1（而非CAPS-1 / 2）通过阻止NSF依赖的去引发作用来稳定引发的突触囊泡。