RIM-BP2 is required for rapid neurotransmitter release through regulation of Ca<sup>2+</sup> channel clustering at hippocampal mossy fiber terminals
RIM-BP2 is required for rapid neurotransmitter release through regulation of Ca<sup>2+</sup> channel clustering at hippocampal mossy fiber terminals
复制标题
RIM-BP2 是通过调节海马苔藓纤维末端 Ca<sup>2</sup> 通道集群来快速释放神经递质所必需的
DOI：
10.1101/2022.08.29.505728
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Sakaba Takeshi
中科院分区：
文献类型：
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作者：
Miyano Rinako;Sakamoto Hirokazu;Hirose Kenzo;Sakaba Takeshi
突触囊泡在突触前活动区（AZ）停靠和融合，这是释放递质的专门场所。AZ蛋白具有多种功能，如钙离子通道的募集以及突触囊泡的对接、启动和融合。然而，每种AZ蛋白类型的确切作用仍然未知。为了剖析RIM-BP 2在哺乳动物皮层突触中具有低释放概率的作用，我们将直接电生理记录和超分辨率成像应用于RIM-BP 2敲除（KO）小鼠的海马苔藓纤维末梢。通过直接突触前记录，我们发现Ca 2+电流减少。兴奋性突触后电流（EPSC）和突触前电容的测量结果表明，RIM-BP 2 KO细胞内Ca 2+内流减少，融合能力受损，导致初始释放概率降低。但较大的Ca 2+内流可部分恢复释放。与突触前记录一致，STED显微镜显示在RIM-BP 2缺陷的AZ处P/Q型Ca 2+通道丰度较低。我们的研究结果表明，RIM-BP 2调节苔藓纤维突触的Ca 2+通道丰度和递质释放。
Synaptic vesicles dock and fuse at the presynaptic active zone (AZ), the specialized site for transmitter release. AZ proteins play multiple roles such as recruitment of Ca 2+ channels as well as synaptic vesicle docking, priming, and fusion. However, the precise role of each AZ protein type remains unknown. In order to dissect the role of RIM-BP2 at mammalian cortical synapses having low release probability, we applied direct electrophysiological recording and super-resolution imaging to hippocampal mossy fiber terminals of RIM-BP2 knockout (KO) mice. By using direct presynaptic recording, we found the reduced Ca 2+ currents. The measurements of excitatory postsynaptic currents (EPSCs) and presynaptic capacitance suggested that the initial release probability was lowered because of the reduced Ca 2+ influx and impaired fusion competence in RIM-BP2 KO. Nevertheless, larger Ca 2+ influx restored release partially. Consistent with presynaptic recording, STED microscopy suggested less abundance of P/Q-type Ca 2+ channels at AZs deficient in RIM-BP2. Our results suggest that the RIM-BP2 regulates both Ca 2+ channel abundance and transmitter release at mossy fiber synapses.