Burnashev N, Monyer H, Seeburg P H, Sakmann B
Max-Planck-Institut für medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Germany.
Neuron. 1992 Jan;8(1):189-98. doi: 10.1016/0896-6273(92)90120-3.
Functionally diverse GluR channels of the AMPA subtype are generated by the assembly of GluR-A, -B, -C, and -D subunits into homo- and heteromeric channels. The GluR-B subunit is dominant in determining functional properties of heteromeric AMPA receptors. This subunit exists in developmentally distinct edited and unedited forms, GluR-B(R) and GluR-B(Q), which differ in a single amino acid in transmembrane segment TM2 (Q/R site). Homomeric GluR-B(R) channels expressed in 293 cells display a low divalent permeability, whereas homomeric GluR-B(Q) and GluR-D channels exhibit a high divalent permeability. Mutational analysis revealed that both the positive charge and the size of the amino acid side chain located at the Q/R site control the divalent permeability of homomeric channels. Coexpression of Q/R site arginine- and glutamine-containing subunits generates cells with varying divalent permeabilities depending on the amounts of expression vectors used for cell transfection. Intermediate divalent permeabilities were traced to the presence of both divalent permeant homomeric and impermeant heteromeric channels. It is suggested that the positive charge contributed by the arginine of the edited GluR-B(R) subunit determines low divalent permeability in heteromeric GluR channels and that changes in GluR-B(R) expression regulate the AMPA receptor-dependent divalent permeability of a cell.
AMPA亚型功能多样的GluR通道是由GluR-A、-B、-C和-D亚基组装成同聚体和异聚体通道而产生的。GluR-B亚基在决定异聚体AMPA受体的功能特性方面起主导作用。该亚基以发育上不同的编辑和未编辑形式存在，即GluR-B(R)和GluR-B(Q)，它们在跨膜片段TM2（Q/R位点）的单个氨基酸上有所不同。在293细胞中表达的同聚体GluR-B(R)通道显示出低二价通透性，而同聚体GluR-B(Q)和GluR-D通道则表现出高二价通透性。突变分析表明，位于Q/R位点的氨基酸侧链的正电荷和大小都控制着同聚体通道的二价通透性。含Q/R位点精氨酸和谷氨酰胺的亚基的共表达会产生具有不同二价通透性的细胞，这取决于用于细胞转染的表达载体的量。中等二价通透性可追溯到二价通透的同聚体通道和不通透的异聚体通道的同时存在。有人提出，编辑后的GluR-B(R)亚基的精氨酸所贡献的正电荷决定了异聚体GluR通道的低二价通透性，并且GluR-B(R)表达的变化调节了细胞的AMPA受体依赖性二价通透性。
