Blocking Endocytosis Enhances Short-Term Synaptic Depression under Conditions of Normal Availability of Vesicles
Blocking Endocytosis Enhances Short-Term Synaptic Depression under Conditions of Normal Availability of Vesicles
复制标题
DOI：
10.1016/j.neuron.2013.08.010
复制
发表时间：
2013-10-16
期刊：
影响因子：
16.2
通讯作者：
Klingauf, Juergen
中科院分区：
文献类型：
--
作者：
Hua, Yunfeng;Woehler, Andrew;Klingauf, Juergen
人们普遍认为，网格蛋白介导的内吞作用是小中枢神经系统突触小泡容量有限的突触传递的限速步骤，在高突触传递速率期间导致短期抑制。在这里，我们通过分析突触Hluorin荧光表明，无论刺激频率（5-40 Hz）如何，200个动作电位都会引起相同的囊泡融合累积量，这意味着不存在囊泡重复使用，因为所使用的方法（碱捕获）仅测量第一轮胞吐作用。然而，在阻断所有缓慢或特定的网格蛋白介导的内吞作用后，相同的刺激模式会导致快速的刺激频率依赖性释放抑制。这种形式的抑制并不反映囊泡供应不足，而似乎是囊泡成分从释放位点缓慢清除的结果。我们的研究结果揭示了内吞蛋白除了在内吞作用本身中的明确作用之外，还具有清除释放位点的重要但被忽视的作用。
It is commonly thought that clathrin-mediated endocytosis is the rate-limiting step of synaptic transmission in small CNS boutons with limited capacity for synaptic vesicles, causing short-term depression during high rates of synaptic transmission. Here, we show by analyzing synaptopHluorin fluorescence that 200 action potentials evoke the same cumulative amount of vesicle fusion, irrespective of the frequency of stimulation (5-40 Hz), implying the absence of vesicle reuse, since the method used (alkaline-trapping) measures only first-round exocytosis. After blocking all slow or specifically clathrin-mediated endocytosis, however, the same stimulation patterns cause a rapid stimulation-frequency-dependent release depression. This form of depression does not reflect insufficient vesicle supply, but appears to be the result of slow clearance of vesicular components from the release site. Our findings uncover an important yet overlooked role of endocytic proteins for release site clearance in addition to their well-characterized role in endocytosis itself.