Heteromeric AMPA receptors assemble with a preferred subunit stoichiometry and spatial arrangement

Heteromeric AMPA receptors assemble with a preferred subunit stoichiometry and spatial arrangement
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DOI:
10.1016/s0896-6273(01)00520-7
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发表时间:
2001-12-06
期刊:
影响因子:
16.2
通讯作者:
Rosenmund, C
Rosenmund, C
中科院分区:
医学1区
文献类型:
--
作者:
Mansour, M;Nagarajan, N;Rosenmund, C

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AMPA受体被认为是亚基GluR 1 -4的四聚体组装体。我们已经研究了两个共表达的亚基(GluR 1/2)是否随机联合收割机形成通道,或优先组装与特定的化学计量和空间构型。亚基进行标记控制离子渗透和脱敏,这些属性进行了监测的相对表达水平和亚基组成的函数。同源受体组装随机而异源受体优先形成的化学计量的两个GluR 1和两个GluR 2亚基,并与相同的亚基位于通道孔的相对侧。如果GluR 1在受体组装过程中比其他亚基组合更快地与GluR 2结合,则这种结构将占主导地位。选择性异聚体组装的实际结果是体内更同质的受体群体。
AMPA receptors are thought to be a tetrameric assembly of the subunits GluR1-4. We have examined whether two coexpressed subunits (GluR1/2) combine at random to form channels, or preferentially assemble with a specific stoichiometry and spatial configuration. The subunits carried markers controlling ion permeation and desensitization, and these properties were monitored as a function of relative expression level and subunit composition. Homomeric receptors assembled stochastically while heteromeric receptors preferentially formed with a stoichiometry of two GluR1 and two GluR2 subunits, and with identical subunits positioned on opposite sides of the channel pore. This structure will predominate if GluR1 binds to GluR2 more rapidly during receptor assembly than other subunit combinations. The practical outcome of selective heteromeric assembly is a more homogenous receptor population in vivo.