Mishima Tatsuya, Fujiwara Tomonori, Sanada Masumi, Kofuji Takefumi, Kanai-Azuma Masami, Akagawa Kimio
Department of Cell Physiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Radio Isotope Laboratory, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
PLoS One. 2014 Feb 28;9(2):e90004. doi: 10.1371/journal.pone.0090004. eCollection 2014.
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.
两种 syntaxin 1（STX1）异构体，即 HPC-1/STX1A 和 STX1B，在神经元中共同表达，并作为神经元靶膜（t）-SNARE 发挥作用。然而，它们在突触传递中的功能差异却鲜为人知。STX1A 基因敲除突变小鼠发育正常，在快速突触传递中未表现出异常，但单胺能传递受损。在本研究中，我们发现 STX1B 基因敲除突变小鼠在出生后 2 周内死亡。为了研究 STX1A 和 1B 之间的功能差异，我们分析了 STX1B 基因敲除突变小鼠和 STX1A/1B 双基因敲除突变小鼠中谷氨酸能和γ-氨基丁酸能突触的突触前特性。我们发现，在 STX1B 基因敲除神经元的谷氨酸能和γ-氨基丁酸能突触中自发量子释放的频率较低，诱发的突触后电流的配对脉冲比率显著更高。STX1B 的缺失还加速了谷氨酸能突触中突触小泡的周转，并减小了谷氨酸能和γ-氨基丁酸能突触中易于释放池的大小。此外，STX1A/1B 双基因敲除神经元在谷氨酸能和γ-氨基丁酸能突触中诱发的突触小泡释放减少且不同步。我们的结果表明，尽管 STX1A 和 1B 作为神经元 t-SNARE 具有基本功能，但 STX1B 而非 STX1A 对于快速传递中自发和诱发的突触小泡胞吐作用的调节是必需的。
