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Rab10失活在长时程增强过程中促进AMPA受体转运和树突棘增大。

Rab10 inactivation promotes AMPAR trafficking and spine enlargement during long-term potentiation.

作者信息

Wang Jie, Nishiyama Jun, Parra-Bueno Paula, Okaz Elwy, Oz Goksu, Liu Xiaodan, Watabe Tetsuya, Suponitsky-Kroyter Irena, McGraw Timothy E, Szatmari Erzsebet M, Yasuda Ryohei

机构信息

Department of Neurobiology, Duke University School of Medicine, Durham, NC, 27710, USA.

Neuronal Signal Transduction Group, Max Planck Florida Institute for Neuroscience, Jupiter, FL, 33458, USA.

出版信息

bioRxiv. 2025 May 28:2022.05.17.492345. doi: 10.1101/2022.05.17.492345.

DOI:10.1101/2022.05.17.492345
PMID:40501544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12154598/
Abstract

Rab-dependent membrane trafficking is critical for changing the structure and function of dendritic spines during synaptic plasticity. Here, we developed highly sensitive sensors to monitor Rab protein activity in single dendritic spines undergoing structural long-term potentiation (sLTP) in rodent organotypic hippocampal slices. During sLTP, Rab10 was persistently inactivated (>30 min) in the stimulated spines, whereas Rab4 was transiently activated over ~5 min. Inhibiting or deleting Rab10 enhanced sLTP, electrophysiological LTP and AMPA receptor (AMPAR) trafficking during sLTP. In contrast, disrupting Rab4 impaired sLTP only in the first few minutes, and decreased AMPAR trafficking during sLTP. Thus, our results suggest that Rab10 and Rab4 oppositely regulate AMPAR trafficking during sLTP, and inactivation of Rab10 signaling facilitates the induction of LTP and associated spine structural plasticity.

摘要

Rab 依赖性膜运输对于突触可塑性期间树突棘结构和功能的改变至关重要。在此，我们开发了高灵敏度传感器，以监测啮齿动物海马脑片培养物中经历结构性长时程增强（sLTP）的单个树突棘中的 Rab 蛋白活性。在 sLTP 期间，受刺激的树突棘中的 Rab10 持续失活（>30 分钟），而 Rab4 在约 5 分钟内短暂激活。抑制或缺失 Rab10 可增强 sLTP、电生理 LTP 以及 sLTP 期间的 AMPA 受体（AMPAR）运输。相反，破坏 Rab4 仅在最初几分钟内损害 sLTP，并减少 sLTP 期间的 AMPAR 运输。因此，我们的结果表明，Rab10 和 Rab4 在 sLTP 期间对 AMPAR 运输起相反的调节作用，并且 Rab10 信号的失活促进 LTP 的诱导和相关的树突棘结构可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7caf/12154598/9999eb3190ef/nihpp-2022.05.17.492345v4-f0005.jpg
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