Synaptotagmin 2 Is the Fast Ca(2+) Sensor at a Central Inhibitory Synapse.
Synaptotagmin 2 Is the Fast Ca(2+) Sensor at a Central Inhibitory Synapse.
复制标题
Synaptotagmin 2是中央抑制突触处的快速Ca（2+）传感器。
DOI：
10.1016/j.celrep.2016.12.067
复制
发表时间：
2017-01-17
期刊：
影响因子：
8.8
通讯作者：
Jonas P
中科院分区：
文献类型：
--
作者：
Chen C;Arai I;Satterfield R;Young SM Jr;Jonas P
脑回路中的GABA能突触产生具有亚毫秒潜伏期和时间精度的抑制性输出信号。释放传感器的分子身份是否有助于这些信号传导特性仍不清楚。在这里，我们研究了在GABA能篮细胞（BC）的胞吐作用的Ca ~（2+）传感器浦肯野细胞（PC）的小脑突触。免疫标记表明，BC终端选择性地表达synaptotagmin 2（Syt 2），而synaptotagmin 1（Syt 1）是丰富的兴奋性终端。Syt 2的遗传消除将动作电位诱发的释放降低至约10%，确定Syt 2为BC-PC突触的主要Ca 2+传感器。差异腺病毒介导的救援显示，Syt 2触发释放更短的潜伏期和更高的时间精度和介导更快的囊泡池补充比Syt 1。此外，删除Syt 2严重减少和延迟双突触抑制后平行纤维刺激。因此，选择性地使用Syt 2作为BC-PC突触的释放传感器确保了小脑微电路中快速有效的前馈抑制。Syt 2是小脑GABA能突触快速释放递质的Ca 2+传感器Syt 2以比Syt 1更快的时间过程触发递质释放Syt 2确保比Syt 1更快地补充易释放池Syt 2是小脑微电路中快速前馈抑制所必需的Chen et al.将synaptotagmin 2鉴定为小脑抑制性突触处递质释放的主要Ca 2+传感器。此外，他们证明，synaptotagmin 2触发更快的释放，并确保更快的再填充囊泡池比synaptotagmin 1。
GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. Syt2 is the Ca2+ sensor of fast transmitter release at a cerebellar GABAergic synapse Syt2 triggers transmitter release with faster time course than Syt1 Syt2 ensures faster replenishment of the readily releasable pool than Syt1 Syt2 is essential for fast feedforward inhibition in cerebellar microcircuits Chen et al. identify synaptotagmin 2 as the major Ca2+ sensor of transmitter release at cerebellar inhibitory synapses. Furthermore, they demonstrate that synaptotagmin 2 triggers faster release and ensures faster refilling of the vesicular pool than synaptotagmin 1.