RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses
RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses
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DOI：
10.1073/pnas.1605256113
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发表时间：
2016-10-11
影响因子：
11.1
通讯作者：
Rosenmund, Christian
中科院分区：
文献类型：
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作者：
Grauel, M. Katharina;Maglione, Marta;Rosenmund, Christian
突触小泡和电压门控钙通道(CAV)的紧密空间耦合确保了动作电位触发的神经递质从突触前活动区(AZs)释放。RAB相互作用分子结合蛋白(RIM-BPS)与钙离子通道相互作用，并通过RIM与释放机制的其他组件相互作用。虽然人类RIM-BPS与自闭症谱系障碍有关，但对哺乳动物RIM-BPS在突触传递中的作用知之甚少。我们在培养和切片中研究了RIM-BP2缺陷的小鼠海马神经元。在两个模型系统中，短期促进作用都显著增强。在培养中的详细分析显示，初始释放概率降低，这可能是短期促进作用增加的基础。超分辨显微镜显示AZs的Ca(V)2.1聚集性受损，这可能改变了释放部位的钙纳米结构域，从而影响了释放概率。RIM-BP1的额外缺失不会加剧这些突触的表型，表明RIM-BP2是这些突触的主要RIM-BP亚型。
The tight spatial coupling of synaptic vesicles and voltage-gated Ca2+ channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca2+ channels and via RIMwith other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2-deficient murine hippocampal neurons in cultures and slices. Short-term facilitation is significantly enhanced in both model systems. Detailed analysis in culture revealed a reduction in initial release probability, which presumably underlies the increased short-term facilitation. Superresolution microscopy revealed an impairment in Ca(V)2.1 clustering at AZs, which likely alters Ca2+ nanodomains at release sites and thereby affects release probability. Additional deletion of RIM-BP1 does not exacerbate the phenotype, indicating that RIM-BP2 is the dominating RIM-BP isoform at these synapses.