IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses
IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses
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DOI：
10.1016/j.neures.2007.10.013
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发表时间：
2008-02-01
影响因子：
2.9
通讯作者：
Kondo, Hisatake
中科院分区：
文献类型：
--
作者：
Sakagami, Hiroyuki;Sanda, Masashi;Kondo, Hisatake
ADP核糖基化因子6（Arf 6）是一种小的GT3，可能通过肌动蛋白细胞骨架和膜运输的组织来调节树突状细胞的分化。在这里，我们的特点是IQ-ArfGEF/BRAG 1，鸟嘌呤核苷酸交换因子（GEF）的Arf 6，在小鼠大脑。体内Arf pull down实验表明IQ-ArfGEF/BRAG 1比Arf 1更有效地激活Arf 6。IQ-ArfGEF/BRAG 1 mRNA在脑内大量表达，在前脑结构和小脑颗粒细胞中表达量较高。在海马神经元中，IQ-ArfGEF/BRAG 1 mRNA不仅定位于神经元细胞体，而且定位于树突状突起，表明其树突状转运和定位。免疫沉淀和体外结合实验表明，IQ-ArfGEF/BRAG 1通过与突触后密度（PSD）支架蛋白PSD-95相互作用，与N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体形成蛋白复合物。免疫组织化学分析表明，IQ-ArfGEF/BRAG 1优先定位于突触后密度的不对称突触的树突棘，但缺乏在GABAA受体携带抑制性突触。总之，IQ-ArfGEF/BRAG 1在兴奋性突触处形成含有PSD-95和NMDA受体的突触后蛋白复合物，在那里它可以作为Arf 6的GEF。(C)2007年由Elsevier爱尔兰有限公司和日本神经科学学会出版。
ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates dendritic differentiation possibly through the organization of actin cytoskeleton and membrane traffic. Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1. IQ-ArfGEF/BRAG1 mRNA was abundantly expressed in the brain with higher levels in forebrain structures and cerebellar granule cells. In hippocampal neurons, IQ-ArfGEF/BRAG1 mRNA was localized not only at neuronal cell bodies but also at dendritic processes, indicating its dendritic transport and localization. Immunoprecipitation and in vitro binding experiments revealed that IQ-ArfGEF/BRAG1 formed a protein complex with N-methyl-D-aspartate (NMDA)-type glutamate receptors through the interaction with a postsynaptic density (PSD) scaffold protein, PSD-95. Immunohistochemical analysis demonstrated that IQ-ArfGEF/BRAG1 was localized preferentially at the postsynaptic density of asymmetrical synapses on dendritic spines, but was lacking at GABAA receptor-carrying inhibitory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6. (C) 2007 Published by Elsevier Ireland Ltd and the Japan Neuroscience Society.