Rapid and reversible fluorescent probe enables repeated snapshot imaging of AMPA receptors during synaptic plasticity

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-06-06 DOI:10.1126/sciadv.adt6683

Kyohei Soga, Takaaki Fujiwara, Mayu Nakagawa, Akihiro Shibata, Hansel Adriel, Kenji Yatsuzuka, Wataru Kakegawa, Michisuke Yuzaki, Itaru Hamachi, Eriko Nango, Shigeki Kiyonaka

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Abstract

The subcellular localization of neurotransmitter receptors is strictly regulated in neurons. Changes in the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–type glutamate receptors (AMPARs) play an essential role in synaptic plasticity, which is the cellular basis of learning and memory. To explore receptor trafficking, genetically encoded approaches (e.g., the fusion of fluorescent proteins to receptors) are often used. However, concerns remain that genetic approaches cannot fully reproduce the receptor functions that are inherent to neurons. Herein, we report on PFQX1(AF488), a fluorescent probe for the visualization of cell-surface AMPARs without any genetic manipulation to neurons. The rapid and reversible staining features of this probe enabled snapshot imaging, which showed the accumulation of native AMPARs in dendritic spines during synaptic plasticity. Moreover, the mechanism of this synaptic accumulation, for which genetically encoded approaches have given controversial results, was revealed by integrating two chemical methods: PFQX1(AF488) and covalent chemical labeling.

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快速和可逆的荧光探针使AMPA受体在突触可塑性期间的重复快照成像

神经递质受体的亚细胞定位在神经元中受到严格调控。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体（AMPARs）转运的变化在突触可塑性中起着重要作用，而突触可塑性是学习和记忆的细胞基础。为了探索受体运输，通常使用遗传编码方法（例如，荧光蛋白与受体的融合）。然而，人们仍然担心遗传方法不能完全再现神经元固有的受体功能。在此，我们报道了PFQX1(AF488)，这是一种用于可视化细胞表面ampar的荧光探针，无需对神经元进行任何遗传操作。该探针的快速和可逆染色特性使快照成像能够显示突触可塑性期间树突棘中天然ampar的积累。此外，通过整合两种化学方法：PFQX1（AF488）和共价化学标记，揭示了这种突触积累的机制，遗传编码方法给出了有争议的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.