Role of α2δ-3 in regulating calcium channel localization at presynaptic active zones during homeostatic plasticity.
Role of α2δ-3 in regulating calcium channel localization at presynaptic active zones during homeostatic plasticity.
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DOI：
10.3389/fnmol.2023.1253669
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发表时间：
2023
影响因子：
4.8
通讯作者：
Wang, Tingting
中科院分区：
文献类型：
--
作者：
Zhang, Yanfeng;Wang, Ting;Cai, Yimei;Cui, Tao;Kuah, Michelle;Vicini, Stefano;Wang, Tingting
关键词：
突触传递的稳态调节是一种进化上保守的机制，对于稳定神经系统至关重要。在果蝇神经肌肉接头（NMJ），突触前稳态增强（PHP）补偿由于药物阻断或遗传缺失引起的突触后谷氨酸受体的损伤。在PHP期间，突触前神经递质释放增加，抵消突触后变化并将兴奋恢复到基线水平。以往的研究表明，α2δ-3是电压门控钙通道（VGCC）的辅助亚基，对PHP在果蝇NMJ的快速诱导和持续表达至关重要。然而，α2δ-3调节PHP期间神经递质释放的分子机制仍有待阐明。在这项研究中，我们利用电生理，共聚焦成像和超分辨率成像方法来探索α2δ-3如何调节PHP期间的突触传递。我们的研究结果表明，α2δ-3通过控制突触前释放位点或活动区的钙通道孔形成α1亚基的定位来控制PHP。此外，我们还研究了α2δ-3内的两个结构域在调节神经递质释放和钙通道定位中的作用。我们的研究结果强调，α2δ-3中的这些结构域在控制突触传递和突触前钙通道丰度方面具有不同的功能，在基线无扰动和PHP期间。总之，我们的研究提供了令人信服的证据，证明α2δ-3是控制钙通道运输和稳态可塑性稳定的不可或缺的信号成分。
The homeostatic modulation of synaptic transmission is an evolutionarily conserved mechanism that is critical for stabilizing the nervous system. At the Drosophila neuromuscular junction (NMJ), presynaptic homeostatic potentiation (PHP) compensates for impairments in postsynaptic glutamate receptors due to pharmacological blockade or genetic deletion. During PHP, there is an increase in presynaptic neurotransmitter release, counteracting postsynaptic changes and restoring excitation to baseline levels. Previous studies have shown that α2δ-3, an auxiliary subunit of voltage-gated calcium channels (VGCCs), is essential for both the rapid induction and sustained expression of PHP at the Drosophila NMJ. However, the molecular mechanisms by which α2δ-3 regulates neurotransmitter release during PHP remain to be elucidated. In this study, we utilized electrophysiological, confocal imaging, and super-resolution imaging approaches to explore how α2δ-3 regulates synaptic transmission during PHP. Our findings suggest that α2δ-3 governs PHP by controlling the localization of the calcium channel pore-forming α1 subunit at presynaptic release sites, or active zones. Moreover, we examined the role of two structural domains within α2δ-3 in regulating neurotransmitter release and calcium channel localization. Our results highlight that these domains in α2δ-3 serve distinct functions in controlling synaptic transmission and presynaptic calcium channel abundance, at baseline in the absence of perturbations and during PHP. In summary, our research offers compelling evidence that α2δ-3 is an indispensable signaling component for controlling calcium channel trafficking and stabilization in homeostatic plasticity.
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影响因子：
64.8
作者：
Chen, Zhou;Mondal, Abhisek;Minor Jr, Daniel L. L.
通讯作者：
Minor Jr, Daniel L. L.
影响因子：
5.3
作者：
Barclay, J;Balaguero, N;Rees, M
通讯作者：
Rees, M
影响因子：
7.8
作者：
Ly, Cindy V.;Yao, Chi-Kuang;Verstreken, Patrik;Ohyama, Tomoko;Bellen, Hugo J.
通讯作者：
Bellen, Hugo J.
突触前电压门控钙通道的功能。
DOI：
10.1093/function/zqaa027
发表时间：
2021
期刊：
Function (Oxford, England)
影响因子：
--
作者：
Dolphin AC
通讯作者：
Dolphin AC
DOI：
10.1126/science.1179685
发表时间：
2009-11-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dickman DK;Davis GW
通讯作者：
Davis GW