M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit
M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit
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M1 毒蕈碱受体通过与 AMPA 受体 GluA1 亚基相互作用促进认知功能。
DOI：
10.1096/fj.201800029r
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发表时间：
2018-08-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Hong-Zhuan
中科院分区：
文献类型：
--
作者：
Zhao, Lan-Xue;Ge, Yan-Hui;Chen, Hong-Zhuan
M1毒蕈碱乙酰胆碱受体（M1 mAChRs）是海马中最丰富的毒蕈碱受体，具有促进认知的作用。AMPA受体（AMPARs）是谷氨酸受体的一个重要亚型，是神经认知网络的重要组成部分。然而，AMPARs在M1 mAChRs的前认知效应中的作用以及M1 mAChRs如何影响AMPARs的功能仍然知之甚少。在这里，我们发现AMPARs的一个亚基GluA1的基本表达及其Ser845位点的磷酸化通过M1 mAChR活性维持。M1 machr的激活促进了GluA1的膜插入，特别是突触后密度。M1 mAChRs拮抗剂对海马依赖性学习记忆的损害与GluA1表达的减少平行，M1 mAChRs激活对学习记忆的改善伴随着GluA1的突触插入及其Ser845位点磷酸化的增加。此外，去除GluA1的Ser845残基磷酸化会削弱M1介导的学习和记忆改善。综上所述，这些结果表明M1 machr和GluA1的功能相关性以及GluA1在M1 machr介导的认知改善中的重要作用。赵,L.-X。， Ge, y - h。，熊昌辉。，唐，李，燕，y.h。，法律，p.y。，邱艳，陈宏志。M1毒蕈碱受体通过与AMPA受体GluA1亚基相互作用促进认知功能。
M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.