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首页> 外文期刊>Neuron >Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse.
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Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse.

机译:Septins调节从Ca(2+)流入微区到纳米区耦合到中央突触释放神经递质的发展转换。

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摘要

Neurotransmitter release depends critically on close spatial coupling of Ca(2+) entry to synaptic vesicles at the nerve terminal; however, the molecular substrates determining their physical proximity are unknown. Using the calyx of Held synapse, where "microdomain" coupling predominates at immature stages and developmentally switches to "nanodomain" coupling, we demonstrate that deletion of the filamentous protein Septin 5 imparts immature synapses with striking morphological and functional features reminiscent of mature synapses. This includes synaptic vesicles tightly localized to active zones, resistance to the slow Ca(2+) buffer EGTA and a reduced number of Ca(2+) channels required to trigger single fusion events. Disrupting Septin 5 organization acutely transforms microdomain to nanodomain coupling and potentiates quantal output in immature wild-type terminals. These observations suggest that Septin 5 is a core molecular substrate that differentiates distinct release modalities at the central synapse.
机译:神经递质的释放关键取决于Ca(2+)进入神经末梢的突触小泡的紧密空间耦合;然而,决定它们物理接近性的分子底物是未知的。使用保持突触的花萼,其中“微结构域”偶联在未成熟阶段占主导地位,并发展到“纳米结构域”偶联,我们证明丝状蛋白Septin 5的缺失赋予未成熟突触以惊人的形态和功能特征,使人联想到成熟的突触。这包括紧密定位于活动区的突触囊泡,对慢速Ca(2+)缓冲液EGTA的抵抗力和触发单个融合事件所需的减少数量的Ca(2+)通道。破坏Septin 5的组织会迅速将微域转换为纳米域耦合,并增强未成熟野生型末端的定量输出。这些观察结果表明,Septin 5是核心分子底物,其在中央突触处区分不同的释放方式。

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