Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.
Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.
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DOI：
10.1371/journal.pone.0090004
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Akagawa K
中科院分区：
文献类型：
--
作者：
Mishima T;Fujiwara T;Sanada M;Kofuji T;Kanai-Azuma M;Akagawa K
突触融合蛋白1（syntaxin 1，STX 1）的两种亚型HPC-1/STX 1A和STX 1B在神经元中共表达，并作为神经元靶膜（t）-SNARE发挥作用。然而，很少有人知道它们在突触传递中的功能差异。STX 1A无效突变小鼠发育正常，在快速突触传递中未显示异常，但单胺能传递受损。在本研究中，我们发现STX 1B无效突变小鼠在出生后2周内死亡。为了研究STX 1A和1B之间的功能差异，我们分析了STX 1B无效突变小鼠和STX 1A/1B双无效突变小鼠中谷氨酸能和GABA能突触的突触前特性。我们发现，自发量子释放的频率较低，诱发突触后电流的成对脉冲比显着更大的STX 1B空神经元的谷氨酸能和GABA能突触。STX 1B的缺失也加速了突触囊泡的周转，并减少了突触囊泡的大小，易于释放池的突触和GABA能突触。此外，STX 1A/1B双空神经元在多巴胺能和GABA能突触中表现出减少的和异步的诱发性突触囊泡释放。我们的研究结果表明，虽然STX 1A和1B共享的基本功能，神经元t-SNARE，STX 1B，而不是STX 1A是必要的自发和诱发的突触囊泡胞吐的快速传输的调节。
Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t)-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.
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