Differential Roles of GluN2B in Two Types of Chemical-induced Long Term Potentiation-mediated Phosphorylation Regulation of GluA1 at Serine 845 in Hippocampal Slices
Differential Roles of GluN2B in Two Types of Chemical-induced Long Term Potentiation-mediated Phosphorylation Regulation of GluA1 at Serine 845 in Hippocampal Slices
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GluN2B 在海马切片中丝氨酸 845 处 GluA1 的两种化学诱导长期增强介导的磷酸化调节中的不同作用
DOI：
10.1016/j.neuroscience.2020.03.012
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发表时间：
2020-03
期刊：
影响因子：
3.3
通讯作者：
Wen Lu
中科院分区：
文献类型：
--
作者：
Bin Zhang;Weiqing Fang;Wu Ma;Fusheng Xue;Heng Ai;Wen Lu
突触可塑性，如长期增强（LTP）和长期抑制（LTD），是学习和记忆的细胞机制的基础。化学诱导的LTP （cLTP）有助于对脑切片或神经元培养物中的分子变化进行生化分析，已被接受为探索突触可塑性的体外模型。无论是福斯克林和罗利普兰（F&R）还是甘氨酸，cLTP都被认为依赖于NMDA受体。然而，对cLTP中NMDA受体的亚单位特异性依赖和调控仍然知之甚少。在本研究中，我们发现f&r诱导的LTP可以调节GluN2B在酪氨酸1472位点的磷酸化水平，而甘氨酸诱导的LTP则不能调节。此外，f&r诱导的LTP而不是甘氨酸诱导的LTP增加了GluA1在845丝氨酸上的磷酸化水平，这依赖于GluN2B的激活，这得到了GluN2B拮抗剂、小干扰肽和crispr - cas9介导的敲除GluN2B的结果的支持。综上所述，我们揭示了GluN2B在f&r诱导的LTP中的重要作用，揭示了NMDA受体GluN2B亚基在特定cLTP中的作用。
Synaptic plasticity, such as long term potentiation (LTP) and long term depression (LTD), underlies the cellular mechanism of learning and memory. Chemical-induced LTP (cLTP), which facilitates biochemical analysis of molecular changes in brain slices or neuronal cultures, has been accepted as an in vitro model to explore synaptic plasticity. cLTP, by either forskolin and rolipram (F&R) or glycine, is thought to be dependent on NMDA receptor. However, subunit-specific dependence and regulation of the NMDA receptor in cLTP remain poorly understood. In the present study, we found that phosphorylation level of GluN2B at tyrosine 1472 was modulated by F&R-induced LTP but not by glycine-induced LTP in hippocampal slices. Furthermore, an increased phosphorylation level of GluA1 at serine 845 by F&R-induced LTP rather than glycine-induced LTP was dependent on the activation of GluN2B, which is supported by the results from GluN2B antagonists, small interfering peptide and CRISPR-Cas9-mediated knock out of GluN2B. Taken together, we reveal the significant role of GluN2B in F&R-induced LTP, uncovering the role of GluN2B subunit of NMDA receptor in a specified cLTP.
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影响因子：
8.3
作者：
Knox R;Brennan-Minnella AM;Lu F;Yang D;Nakazawa T;Yamamoto T;Swanson RA;Ferriero DM;Jiang X
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影响因子：
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通讯作者：
Hardingham, Giles E.
DOI：
10.1098/rstb.2013.0145
发表时间：
2014-01
期刊：
Philosophical Transactions of the Royal Society B: Biological Sciences
影响因子：
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作者：
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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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影响因子：
64.8
作者：
Tang, YP;Shimizu, E;Tsien, JZ
通讯作者：
Tsien, JZ