Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking.
Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking.
复制标题
DOI：
10.1016/j.neuron.2016.07.005
复制
发表时间：
2016-08-17
期刊：
影响因子：
16.2
通讯作者：
Kaeser PS
中科院分区：
文献类型：
--
作者：
Wang SSH;Held RG;Wong MY;Liu C;Karakhanyan A;Kaeser PS
在神经末梢中，突触囊泡的对接和释放被限制在活性区。活性区是一种蛋白质支架，附着在突触前质膜上，与突触后受体相对。在这里，我们产生了去除活性区蛋白RIM和ELKS的条件性敲除小鼠，这另外导致了Munc 13、Bassoon、Piccolo和RIM-BP的丢失，表明活性区的解体。我们观察到几乎完全缺乏突触囊泡对接和囊泡释放概率和胞吐速度的强烈降低，但总囊泡数量，SNARE蛋白水平和突触后密度保持不受影响。尽管引发蛋白Munc 13和RIM和停靠囊泡的损失，可释放囊泡的池仍然存在。因此，活性区是必要的突触囊泡对接和提高释放概率，但可释放的囊泡可以定位远离突触前质膜。
In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane.