Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release.
Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release.
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Fife组织了突触囊泡和钙通道，以释放高概率神经递质。
DOI：
10.1083/jcb.201601098
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发表时间：
2017-01-02
期刊：
影响因子：
--
通讯作者：
O'Connor-Giles KM
中科院分区：
文献类型：
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作者：
Bruckner JJ;Zhan H;Gratz SJ;Rao M;Ukken F;Zilberg G;O'Connor-Giles KM
FIFE是一种短笛短笛-RIM相关蛋白，通过一种未知的机制调节神经传递和运动行为。在这里，布鲁克纳等人。显示FIFE组织突触小泡对接和偶联到钙通道，以建立和调节突触强度。突触连接的强度差异很大，是神经回路内交流的关键决定因素。对建立和调节神经递质释放特性的突触前因子的机械性洞察对于理解突触强度、电路功能和神经可塑性至关重要。我们之前发现了果蝇短笛-RIM相关的FIFE，它通过一种未知的机制调节神经传递和运动行为。在这里，我们证明了FIFE在活动区Cytomatrix定位并与RIM相互作用，以促进神经递质的释放。FIFE的丢失会导致活动区、细胞骨架结构和分子组织的严重破坏。通过电子断层扫描和电生理研究，我们发现，由于与钙通道的偶联受损，准备释放的突触小泡的积累和释放几率减少。最后，我们发现FIFE对于神经传递的动态平衡调节是必不可少的。我们认为，FIFE在钙离子通道簇的纳米距离内组织活动区来创建突触小泡释放部位，以实现可靠和可调节的神经递质释放。
Fife is a Piccolo-RIM–related protein that regulates neurotransmission and motor behavior through an unknown mechanism. Here, Bruckner et al. show that Fife organizes synaptic vesicle docking and coupling to calcium channels to establish and modulate synaptic strength. The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.