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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Selective expression of heteromeric AMPA receptors driven by flip-flop differences.
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Selective expression of heteromeric AMPA receptors driven by flip-flop differences.

机译：由触发器差异驱动的异聚AMPA受体的选择性表达。

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Initial models of AMPA receptor assembly postulated the unrestricted stochastic association of individual subunits. The low Ca(2+) permeability and nonrectified current-voltage relationship of most native AMPA receptors were ascribed to dominant effects of the glutamate receptor 2 (GluR2) subunit. A recent model, however, proposes instead the preferred assembly of GluR1 and GluR2 subunits into tetrameric complexes as pairs of identical heteromeric dimers. To compare unrestricted versus selective models of GluR1 and GluR2 assembly, these subunits, in both flip and flop isoforms, were expressed in varying ratios in human embryonic kidney 293 cells. Coexpression of pairs of wild-type subunits produced expression of a predominance of heteromeric over homomeric receptors. Only a single functional type of heteromeric receptor was observed, indicating a pattern of apparent dominance not only of GluR2 for ion selectivity, but also of the flip isoform for receptor desensitization. Expression of wild-type GluR1 flip, however, with a mutant form of the same subunit carrying an arginine residue at the glutamine/arginine site (GluR1(R) flip) demonstrated a lack of dominance of GluR1(R) in determination of ion selectivity, whereas expression of GluR1(R) flip with GluR1 flop reproduced the pattern of apparent complete dominance. Together, the data support the selective expression of heteromeric receptors and are compatible with an equilibrium model of assembly of tetramers as pairs of identical heteromeric dimers. Expression of co-assemblies of the flip and flop isoforms, like that of the GluR1 and GluR2 subunits, is strongly favored over that of homomeric assemblies.
机译：AMPA受体装配的初始模型假定单个亚基的无限制随机关联。大多数天然AMPA受体的低Ca（2+）渗透性和未整流的电流-电压关系归因于谷氨酸受体2（GluR2）亚基的主要作用。但是，最近的模型提出了将GluR1和GluR2亚基优选组装成四聚体复合物的方法，它们是一对相同的异聚二聚体。为了比较GluR1和GluR2装配的非限制性模型与选择性模型，在人和胚胎同种型中，这些亚基以不同的比例在人类胚胎肾293细胞中表达。成对的野生型亚基的共表达产生异源性高于同源性受体的表达。仅观察到单一功能类型的异聚受体，表明不仅对离子选择性的GluR2，而且对于受体脱敏的翻转同种型的明显优势模式。然而，野生型GluR1 Flip的表达具有在谷氨酰胺/精氨酸位点带有精氨酸残基的相同亚基的突变形式（GluR1（R）Flip），表明在确定离子选择性方面缺少GluR1（R）的优势。 ，而使用GluR1触发器的GluR1（R）触发器的表达则再现了明显的完全优势模式。在一起，数据支持异源受体的选择性表达，并且与四聚体组装成相同的异源二聚体对的平衡模型兼容。像同构组件的表达一样，与GluR1和GluR2亚基类似的翻转和同构异构体的共同组件的表达也受到了强烈的支持。

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