谷氨酸受体 1 的氨基末端结构域通过与神经可塑性蛋白 65 相互作用来介导长时程增强的维持。
The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65.
机构信息
State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, 210032 Nanjing, China.
Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 210032 Nanjing, China.
出版信息
Proc Natl Acad Sci U S A. 2021 Mar 2;118(9). doi: 10.1073/pnas.2019194118.
Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. In this study, using CRISPR/Cas9 to delete the endogenous AMPARs and replace them with the mutant forms in single neurons, we have found that the amino-terminal domain (ATD) of GluA1 is required for LTP maintenance. Moreover, we show that GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65). Neurons lacking Np65 exhibit severely impaired LTP maintenance, and Np65 deletion prevents GluA1 from rescuing LTP in AMPARs-deleted neurons. Thus, our study reveals an essential role for GluA1/Np65 binding in anchoring AMPARs at the postsynaptic membrane during LTP.
长时程增强（LTP）长期以来一直被认为是学习和记忆的重要细胞机制。LTP 的表达涉及 NMDA 受体依赖性 AMPA 受体（AMPARs）的突触内插入。然而，在 LTP 过程中，AMPAR 如何被募集并锚定在突触后膜上仍然知之甚少。在这项研究中，我们使用 CRISPR/Cas9 技术在单个神经元中删除内源性 AMPARs 并将其替换为突变形式，发现 GluA1 的氨基末端结构域（ATD）对于 LTP 的维持是必需的。此外，我们表明 GluA1 ATD 直接与细胞黏附分子神经钙黏蛋白-65（Np65）相互作用。缺乏 Np65 的神经元表现出严重的 LTP 维持受损，而 Np65 的缺失阻止了 GluA1 在 AMPAR 缺失神经元中拯救 LTP。因此，我们的研究揭示了 GluA1/Np65 结合在 LTP 期间将 AMPARs 锚定在突触后膜中的重要作用。
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