SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming
SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming
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DOI：
10.1016/j.neuron.2010.09.019
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发表时间：
2010-11-04
期刊：
影响因子：
16.2
通讯作者：
Rhee, Jeong-Seop
中科院分区：
文献类型：
--
作者：
Burgalossi, Andrea;Jung, Sangyong;Rhee, Jeong-Seop
神经递质的释放是通过钙离子触发的SNARE复合物依赖的突触囊泡融合进行的。融合后，ATP酶NSF及其辅因子α和β SNAP分解SNARE复合物，从而回收单个SNARE用于随后的融合反应。我们研究了α-和β SNAP表达的遗传扰动对突触囊泡胞吐的影响，采用新的Ca 2 + uncaging协议来研究海马神经元小突触囊泡的运输，启动和融合。通过表征该协议，我们表明，同步和异步发射器释放涉及不同的Ca 2+传感器，并没有引起不同的可释放囊泡池，和紧张性发射器释放是由于正在进行的启动和融合的新的突触囊泡在高突触活动。我们对α和β SNAP缺失突变神经元的分析表明，这两种NSF辅因子通过确定游离SNARE组分的可用性来支持突触囊泡启动，特别是在高突触活性阶段。
Neurotransmitter release proceeds by Ca2+-triggered, SNARE-complex-dependent synaptic vesicle fusion. After fusion, the ATPase NSF and its cofactors alpha- and beta SNAP disassemble SNARE complexes, thereby recycling individual SNAREs for subsequent fusion reactions. We examined the effects of genetic perturbation of alpha- and beta SNAP expression on synaptic vesicle exocytosis, employing a new Ca2+ uncaging protocol to study synaptic vesicle trafficking, priming, and fusion in small glutamatergic synapses of hippocampal neurons. By characterizing this protocol, we show that synchronous and asynchronous transmitter release involve different Ca2+ sensors and are not caused by distinct releasable vesicle pools, and that tonic transmitter release is due to ongoing priming and fusion of new synaptic vesicles during high synaptic activity. Our analysis of alpha- and beta SNAP deletion mutant neurons shows that the two NSF cofactors support synaptic vesicle priming by determining the availability of free SNARE components, particularly during phases of high synaptic activity.