Hippocampal Lnx1-NMDAR multiprotein complex mediates initial social memory.
Hippocampal Lnx1-NMDAR multiprotein complex mediates initial social memory.
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海马Lnx1-NMDAR多蛋白复合物介导初始社会记忆
DOI：
10.1038/s41380-019-0606-y
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发表时间：
2021-08
影响因子：
11
通讯作者：
Xu NJ
中科院分区：
文献类型：
--
作者：
Liu XD;Ai PH;Zhu XN;Pan YB;Halford MM;Henkemeyer M;Feng DF;Xu TL;Sun S;Xu NJ
社会互动和交流是进化保守的行为，在哺乳动物中发展，以建立伙伴认知。在人类患者和神经发育障碍的动物模型中，社交能力的缺陷已被代表，这与突触谷氨酸受体和相关PDZ结合蛋白的遗传变异有关。然而，这些关键蛋白如何在细胞水平上专门用于出生后发育阶段的初始社会行为仍然是难以捉摸的。在这里，我们确定了海马CA 3特异性表达的PDZ支架蛋白Lnx 1所需的初始社会行为。通过基因打靶，我们发现Lnx 1缺陷导致幼年小鼠海马神经元活动障碍和伴侣辨别的社会记忆障碍，这些小鼠在成年阶段也表现出认知缺陷。我们进一步证明，Lnx 1缺失导致NMDA受体（NMDAR）功能减退，这是由于PSD隔室中GluN 2B表达减少和Lnx 1-NMDAR-EphB 2复合物的破坏。Lnx 1 −/−小鼠CA 3区Lnx 1或EphB 2蛋白的特异性恢复挽救了有缺陷的突触功能和社会记忆。这些发现揭示了突触后NMDAR多蛋白复合物在调节青少年时期初始社会记忆形成中的关键作用。
Social interaction and communication are evolutionary conserved behaviours that are developed in mammals to establish partner cognition. Deficit in sociability has been represented in human patients and animal models of neurodevelopmental disorders, which are connected with genetic variants of synaptic glutamate receptors and associated PDZ-binding proteins. However, it remains elusive how these key proteins are specialized in the cellular level for the initial social behaviour during postnatal developmental stage. Here we identify a hippocampal CA3 specifically expressed PDZ scaffold protein Lnx1 required for initial social behaviour. Through gene targeting we find that Lnx1 deficiency led to a hippocampal subregional disorder in neuronal activity and social memory impairments for partner discrimination observed in juvenile mice which also show cognitive defects in adult stage. We further demonstrate that Lnx1 deletion causes NMDA receptor (NMDAR) hypofunction and this is attributable to decreased GluN2B expression in PSD compartment and disruption of the Lnx1–NMDAR–EphB2 complex. Specific restoration of Lnx1 or EphB2 protein in the CA3 area of Lnx1−/− mice rescues the defective synaptic function and social memory. These findings thus reveal crucial roles of postsynaptic NMDAR multiprotein complex that regulates the formation of initial social memory during the adolescent period.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
5.3
作者：
Fan X;Jin WY;Wang YT
通讯作者：
Wang YT
影响因子：
64.5
作者：
Henkemeyer, M;Orioli, D;Klein, R
通讯作者：
Klein, R
影响因子：
64.8
作者：
Cui, Guohong;Jun, Sang Beom;Jin, Xin;Pham, Michael D.;Vogel, Steven S.;Lovinger, David M.;Costa, Rui M.
通讯作者：
Costa, Rui M.
影响因子：
25
作者：
Choi, S;Klingauf, J;Tsien, RW
通讯作者：
Tsien, RW