The Expression of Two Splice Variants of Metabotropic Glutamate Receptor Subtype 5 in the Rat Brain and Neuronal Cells During Development

The Expression of Two Splice Variants of Metabotropic Glutamate Receptor Subtype 5 in the Rat Brain and Neuronal Cells During Development
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DOI:
10.1046/j.1471-4159.1995.65041536.x
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发表时间:
1995-10
影响因子:
4.7
通讯作者:
R. Minakami;Ken‐ichiro Iida;Noriko Hirakawa;H. Sugiyama
R. Minakami;Ken‐ichiro Iida;Noriko Hirakawa;H. Sugiyama
中科院分区:
医学2区
文献类型:
--
作者:
R. Minakami;Ken‐ichiro Iida;Noriko Hirakawa;H. Sugiyama

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翻译后摘要:我们以前报道,与额外的氨基酸残基的变体存在于代谢型谷氨酸受体亚型5(mGluR 5)。两种亚型中的任何一种,分别命名为mGluR 5 b和mGluR 5a,当在非洲爪蟾卵母细胞中表达时,会产生Ca 2+激活的Cl−电流。我们在此报告,这两个异构体产生的外显子跳跃型的选择性剪接。在出生后发育过程中进行检查时,观察到大鼠海马和大脑皮层中主要mGluR 5同种型mRNA从mGluR 5a转换为mGluR 5 b。我们还研究了两种可以在体外分化为神经元样细胞的细胞系。尽管在未分化或分化的NG 108 - 15细胞中几乎检测不到mGluR 5 b mRNA,但在P19细胞中诱导分化后,两种变体mRNA的相对量发生了变化。在神经元样P19细胞上的反式-d,l-1-氨基-1,3-环戊烷二羧酸酯的细胞外应用诱导细胞内Ca 2+动员,从而表明细胞可以表达与磷脂酶C偶联的功能性mGluR(s)和可以介导信号转导途径的其他组分。因此,该细胞系可以提供用于在分子水平上研究mGluR 5表达和其他mGluR诱导现象的模型系统。
Abstract: We previously reported that a variant with extra amino acid residues exists in the metabotropic glutamate receptor subtype 5 (mGluR5). Either of the two isoforms, named mGluR5b and mGluR5a for the isoforms with and without the inserted sequence, respectively, generated Ca2+‐activated Cl− current when expressed in Xenopus oocytes. We herein report that these two isoforms are produced by the alternative splicing of the exon skipping type. When examined during the course of postnatal development, the major mGluR5 isotype mRNA was observed to switch from mGluR5a to mGluR5b in the rat hippocampus and the cerebral cortex. We also investigated two cell lines that could be differentiated into neuron‐like cells in vitro. Whereas the mGluR5b mRNA was hardly detectable in either undifferentiated or differentiated NG108‐15 cells, the relative amounts of the two variant mRNAs changed after the induction of differentiation in the P19 cells. An extracellular application of trans‐d,l‐1‐amino‐1,3‐cyclopentanedicarboxylate on the neuron‐like P19 cells induced intracellular Ca2+ mobilization, thus suggesting that the cells could express functional mGluR(s) coupled to phospholipase C and other components that could mediate the signal transduction pathway. This cell line may thus provide a model system for studying both mGluR5 expression and other mGluR‐induced phenomena at the molecular level.