Brain-specific potential guanine nucleotide exchange factor for Arf, synArfGEF (Po), is localized to postsynaptic density
Brain-specific potential guanine nucleotide exchange factor for Arf, synArfGEF (Po), is localized to postsynaptic density
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DOI：
10.1111/j.1471-4159.2004.02440.x
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发表时间：
2004-06-01
影响因子：
4.7
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Inaba, Y;Tian, QB;Suzuki, T
我们从大鼠脑cDNA文库中克隆出一种新的cDNA，根据其结构域及定位，将其命名为一种潜在的Arf突触鸟嘌呤核苷酸交换因子（GEF），即synArfGEF (Po)（基因库登录号AB057643）。克隆得到的基因长度为7410个碱基，编码序列长3585个碱基对，编码一种含1194个氨基酸的蛋白质。推导得出的该蛋白质在N端部分含有卷曲螺旋结构，之后依次是Sec7结构域和普列克底物蛋白同源（PH）结构域。因此，该蛋白质属于Sec7家族蛋白，即鸟嘌呤核苷酸交换因子。ADP - 核糖基化因子（Arf）结合序列的保守性表明，该蛋白质是Arf的鸟嘌呤核苷酸交换因子。该基因在脑中特异性表达，且呈现区域特异性表达。在从大鼠前脑制备的突触后致密物（PSD）组分中，这种蛋白质高度富集。独特的是，该蛋白质通过其C端PDZ结合基序与PSD - 95、SAP97以及Homer/Vesl 1/PSD - Zip45相互作用，并在培养的皮质神经元中与这些蛋白质共定位。这些结果支持其定位于突触后致密物。对大鼠脑进行的免疫组化检测也证实了其突触后定位。synArfGEF的mRNA不仅定位于神经元细胞的胞体，还定位于树突。因此，mRNA和蛋白质均定位于突触后区室。这些结果表明，synArfGEF在大脑的突触后发挥作用。
We cloned from a rat brain cDNA library a novel cDNA and named it a potential synaptic guanine nucleotide exchange factor (GEF) for Arf (synArfGEF (Po)) (GenBank Accession no. AB057643) based on its domain structure and localization. The cloned gene was 7410 bases long with a 3585-bp coding sequence encoding a protein of 1194 amino acids. The deduced protein contained a coiled-coil structure in the N-terminal portion followed by Sec7 and Plekstrin homology (PH) domains. Thus, the protein was a member of the Sec7 family of proteins, GEFs. Conservation of the ADP-ribosylation factor (Arf)-binding sequence suggested that the protein was a GEF for Arf. The gene was expressed specifically in the brain, where it exhibited region-specific expression. The protein was highly enriched in the postsynaptic density (PSD) fraction prepared from the rat forebrain. Uniquely, the protein interacted with PSD-95, SAP97 and Homer/Vesl 1/PSD-Zip45 via its C-terminal PDZ-binding motif and co-localized with these proteins in cultured cortical neurons. These results supported its localization in the PSD. The postsynaptic localization was also supported by immunohistochemical examination of the rat brain. The mRNA for the synArfGEF was also localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the postsynaptic compartments. These results suggest a postsynaptic role of synArfGEF in the brain.