Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction.
Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction.
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DOI：
10.1016/s0021-9258(17)42247-2
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发表时间：
1994-01
期刊：
影响因子：
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通讯作者：
Naoyuki Okamoto;S. Hori;C. Akazawa;Y. Hayashi;R. Shigemoto;N. Mizuno;S. Nakanishi
中科院分区：
文献类型：
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作者：
Naoyuki Okamoto;S. Hori;C. Akazawa;Y. Hayashi;R. Shigemoto;N. Mizuno;S. Nakanishi
使用代谢型受体 (mGluR) 家族中保守的引物序列，通过聚合酶链式反应介导的 DNA 扩增，并随后筛选大鼠前脑 cDNA 文库，分离出一种名为 mGluR7 的新型大鼠代谢型谷氨酸受体的 cDNA 克隆。克隆的 mGluR7 亚型由 915 个氨基酸残基组成，并表现出 mGluR 家族共有的结构体系，在七个假定的跨膜结构域之前有一个大的细胞外结构域。 mGluR7 在 mGluR 家族成员中显示出与 mGluR4 和 mGluR6 最高的序列相似性。与 mGluR4 和 mGluR6 类似，mGluR7 响应激动剂相互作用，抑制毛喉素刺激的环 AMP 积累，并与用克隆 cDNA 转染的中国仓鼠卵巢细胞中的 L-2-氨基-4-磷酸丁酸和 L-丝氨酸-O-磷酸发生有效反应。 mGluR7 mRNA 的 RNA 印迹和原位杂交分析表明，它在中枢神经系统的许多神经元细胞中广泛表达，因此与表达更为有限的 mGluR4 或 mGluR6 mRNA 不同。因此，mGluR7 与 mGluR4 一起对应于假定的 L-2-氨基-4-磷酸丁酸受体，其在调节中枢神经系统中谷氨酸传输中发挥重要作用。
A cDNA clone for a new rat metabotropic glutamate receptor termed mGluR7 was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic receptor (mGluR) family and by the subsequent screening of a rat forebrain cDNA library. The cloned mGluR7 subtype consists of 915 amino acid residues and exhibits a structural architecture common to the mGluR family with a large extracellular domain preceding the seven putative membrane-spanning domains. mGluR7 shows the highest sequence similarity to mGluR4 and mGluR6 among the members of the mGluR family. Similar to mGluR4 and mGluR6, mGluR7 inhibits forskolin-stimulated cyclic AMP accumulation in response to agonist interaction and potently reacts with L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate in Chinese hamster ovary cells transfected with the cloned cDNA. RNA blot and in situ hybridization analyses of mGluR7 mRNA indicated that it is widely expressed in many neuronal cells of the central nervous system and is thus different from the more limitedly expressed mGluR4 or mGluR6 mRNA. mGluR7 together with mGluR4 thus corresponds to the putative L-2-amino-4-phosphonobutyrate receptor which plays an important role in modulation of glutamate transmission in the central nervous system.