Glutamate-induced δ-catenin redistribution and dissociation from postsynaptic receptor complexes
Glutamate-induced δ-catenin redistribution and dissociation from postsynaptic receptor complexes
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DOI：
10.1016/s0306-4522(02)00532-8
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Lu, Q
中科院分区：
文献类型：
--
作者：
Jones, SB;Lanford, GW;Lu, Q
β-连环蛋白(又称神经斑相关臂重复蛋白/神经链)主要是p120(CTN)亚家族中的大脑特异成员，在神经元发育中发挥重要作用。我们以前的研究表明，Delta-Catenin的异位表达诱导了树突样延伸的形成，并且Delta-Catenin的过表达促进了树突状分支的形成，增加了脊椎的密度。在这里，我们证明了Delta-catenin在成年小鼠脑中呈现树突分布模式，并与突触后密度-95(PSD-95)在洗涤剂不可溶突触后支架中共富集。在体内，Delta-catenin与兴奋性神经递质受体包括N-甲基-D-天冬氨酸受体2A(NR2A)、代谢性谷氨酸受体1α(MGluR1pha)以及PSD-95形成稳定的复合体。在培养的原代胚胎神经元中，Delta-catenin簇与丝状肌动蛋白共同分布，并抵抗洗涤剂的提取。在过度表达β-连环蛋白的海马神经元中，谷氨酸刺激导致β-连环蛋白的迅速重新分布，这种重新分布可被离子型谷氨酸受体的选择性抑制剂6-氰基-7-硝基-2，3-二酮和地佐西平所减弱。谷氨酸受体激活后，β-连环蛋白表达下调，与NR2A和mGluR1α的相关性减弱。这些发现支持在神经元发育过程中，β-连环蛋白与谷氨酸能兴奋性突触信号通路之间可能存在功能联系。(C)2002年IBRO。爱思唯尔科学有限公司出版。版权所有。
delta-Catenin (or neural plakophilin-related arm-repeat protein/neurojungin) is primarily a brain specific member of the p120(ctn) subfamily of armadillo/beta-catenin proteins that play important roles in neuronal development. Our previous studies have shown that the ectopic expression of delta-catenin induces the formation of dendrite-like extensions and that the overexpression of delta-catenin promotes dendritic branching and increases spine density. Here we demonstrate that delta-catenin displays a dendritic distribution pattern in the adult mouse brain and is co-enriched with postsynaptic density-95 (PSD-95) in the detergent insoluble postsynaptic scaffolds. delta-Catenin forms stable complexes with excitatory neurotransmitter receptors including ionotropic N-methyl-D-aspartic acid receptor 2A (NR2A), metabotropic glutamate receptor 1alpha (mGluR1alpha), as well as PSD-95 in vivo. In cultured primary embryonic neurons, delta-catenin clusters co-distribute with filamentous actin and resist detergent extraction. In dissociated hippocampal neurons overexpressing delta-catenin, glutamate stimulation leads to a rapid redistribution of delta-catenin that can be attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione and dizocilpine, selective inhibitors of ionotropic glutamate receptors. Upon glutamate receptor activation, delta-catenin becomes down-regulated and its association with NR2A and mGluR1alpha in cultured neurons is diminished.These findings support a possible functional connection between delta-catenin and the glutamatergic excitatory synaptic signaling pathway during neuronal development. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.