The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons
The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons
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DOI：
10.1016/j.febslet.2005.10.051
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发表时间：
2005-12-05
期刊：
影响因子：
3.5
通讯作者：
Colicos, MA
中科院分区：
文献类型：
--
作者：
Khosravani, H;Altier, C;Colicos, MA
突触介导神经元之间的通信，因此在中枢神经系统的信息处理中起着基础作用。神经连接素形成异嗜性突触细胞粘附分子家族，并且神经连接素1（NL 1）已被证明参与兴奋性突触的形成，并且已被提出通过与PSD 95共同结合而间接与NMDA受体缔合。在自闭症患者中发现的神经连接素3（Arg 451 Cys-NL 3，人类序列编号）突变与脊柱密度改变有关，并降低了与突触前伴侣P-neurexin的结合能力。在这里，我们研究了NL 1和同源NL 1突变Arg 473 Cys-NL 1（R473 C-NL 1）在兴奋性突触传递和NMDA受体分布中的作用。我们证明，R473 C-NL 1，当在培养的海马神经元中表达时，可以诱导NMDA电流幅度的急剧增加，并且这种变化伴随着突触后细胞中的NMDA受体聚集。(c)2005年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Synapses mediate communication between neurons, thus playing a fundamental role in information processing in the CNS. Neuroligins form a family of heterophilic synaptic cell adhesion molecules, and neuroligin 1 (NL1) has been shown to be involved in the formation of excitatory synapses and have been suggested to associate indirectly with NMDA receptors by common binding to PSD95. A mutation in neuroligin 3 (Arg451Cys-NL3, human sequence numbering) identified in autistic patients is associated with altered spine density and has reduced binding capacity for its presynaptic partner P-neurexin. Here, we investigated the role of NL1 and the homologous NL1 mutation Arg473Cys-NL1 (R473C-NL1) in excitatory synaptic transmission and NMDA receptor distribution. We demonstrate that R473C-NL1, when expressed in cultured hippocampal neurons, can induce a dramatic increase in NMDA current amplitude and that this change is accompanied by NMDA receptor clustering in the postsynaptic cell. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.