Nano-organization of spontaneous GABAergic transmission directs its autonomous function in neuronal signaling.
Nano-organization of spontaneous GABAergic transmission directs its autonomous function in neuronal signaling.
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DOI：
10.1016/j.celrep.2022.111172
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发表时间：
2022-08-09
期刊：
影响因子：
8.8
通讯作者：
Kavalali, Ege T.
中科院分区：
文献类型：
--
作者：
Guzikowski, Natalie J.;Kavalali, Ege T.
早期的研究描绘了在兴奋性突触处驱动神经递质释放和突触后信号传导的蛋白质的精确排列。然而，在抑制性突触的神经传递的空间组织仍然不清楚。在这里，我们利用抗疟青蒿素和抑制性突触支架蛋白，桥蛋白的分子特异性相互作用，探测中枢突触中γ-氨基丁酸A受体（GABAAR）介导的神经传递的功能组织。短期应用青蒿素会严重收缩桥蛋白和GABAaR γ2亚基簇的大小和密度。这种尺寸收缩引起Bdnf表达的神经元活性非依赖性增加，这是由于GABA能自发性而非诱发性神经传递的特异性减少。同样的功能效应可以通过破坏连接桥蛋白和神经元细胞骨架的微管来模拟。这些结果表明，GABA能突触后装置具有一个同心的中心-周围组织，其中周围的桥蛋白簇选择性地维持自发的GABA能神经传递，促进其自主功能调节BDNF的表达。Guzikowski和Kavalali利用抗疟青蒿素和抑制性突触支架蛋白（gephyrin）的分子特异性相互作用，来探测GABAAR介导的神经传递的功能组织。他们的研究探索了GABA能突触的纳米组织以及诱发和自发神经传递的分离。
Earlier studies delineated the precise arrangement of proteins that drive neurotransmitter release and post-synaptic signaling at excitatory synapses. However, spatial organization of neurotransmission at inhibitory synapses remains unclear. Here, we took advantage of the molecularly specific interaction of antimalarial artemisinins and the inhibitory synapse scaffold protein, gephyrin, to probe the functional organization of gamma-aminobutyric acid A receptor (GABAAR)-mediated neurotransmission in central synapses. Short-term application of artemisinins severely contracts the size and density of gephyrin and GABAaR γ2 subunit clusters. This size contraction elicits a neuronal activity-independent increase in Bdnf expression due to a specific reduction in GABAergic spontaneous, but not evoked, neurotransmission. The same functional effect could be mimicked by disruption of microtubules that link gephyrin to the neuronal cytoskeleton. These results suggest that the GABAergic postsynaptic apparatus possesses a concentric center-surround organization, where the periphery of gephyrin clusters selectively maintains spontaneous GABAergic neurotransmission facilitating its autonomous function regulating Bdnf expression. Guzikowski and Kavalali took advantage of the molecularly specific interaction of antimalarial artemisinins and an inhibitory synapse scaffold protein, gephyrin, to probe the functional organization of GABAAR-mediated neurotransmission. Their study explores the nano-organization of the GABAergic synapse and the segregation of evoked and spontaneous neurotransmission.
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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期刊：
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