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R/G editing in GluA2Rflop modulates the functional difference between GluA1 flip and flop variants in GluA1/2R heteromeric channels.
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Oct-20 , DOI: 10.1038/s41598-017-13233-2
Wei Wen , Chi-Yen Lin , Li Niu

In α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors, RNA editing and alternative splicing generate sequence variants, and those variants, as in GluA2-4 AMPA receptor subunits, generally show different properties. Yet, earlier studies have shown that the alternatively spliced, flip and flop variants of GluA1 AMPA receptor subunit exhibit no functional difference in homomeric channel form. Using a laser-pulse photolysis technique, combined with whole-cell recording, we measured the rate of channel opening, among other kinetic properties, for a series of AMPA channels with different arginine/glycine (R/G) editing and flip/flop status. We find that R/G editing in the GluA2 subunit modulates the channel properties in both homomeric (GluA2Q) and complex (GluA2Q/2R and GluA1/2R) channel forms. However, R/G editing is only effective in flop channels. Specifically, editing at the R/G site on the GluA2R flop isoform accelerates the rate of channel opening and desensitization for GluA1/2R channels more pronouncedly with the GluA1 being in the flop form than in the flip form; yet R/G editing has no effect on either channel-closing rate or EC50. Our results suggest R/G editing via GluA2R serve as a regulatory mechanism to modulate the function of GluA2R-containing, native receptors involved in fast excitatory synaptic transmission.

中文翻译:

GluA2Rflop中的R / G编辑可调节GluA1 / 2R异源通道中GluA1触发器和触发器变体之间的功能差异。

在α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AMPA)受体中,RNA编辑和选择性剪接产生序列变体,而这些变体,如在GluA2-4 AMPA受体亚基中一样,通常表现出不同的特性。然而,较早的研究表明,GluA1 AMPA受体亚基的可变剪接,翻转和翻转变体在同型通道形式上没有功能差异。使用激光脉冲光解技术,结合全细胞记录,我们测量了具有不同精氨酸/甘氨酸(R / G)编辑和翻转/翻转状态的一系列AMPA通道的通道打开速率以及其他动力学特性。我们发现,在GluA2亚基中进行R / G编辑可调节同质(GluA2Q)和复杂(GluA2Q / 2R和GluA1 / 2R)通道形式的通道特性。然而,R / G编辑仅在触发器通道中有效。具体而言,在GluA2R触发器同种型的R / G位置进行编辑可加快GluA1 / 2R通道的通道打开和脱敏速度,其中GluA1处于触发器形式而不是翻转形式。R / G编辑对通道关闭率或EC都没有影响50。我们的结果表明,通过GluA2R进行R / G编辑可作为调节机制,以调节参与快速兴奋性突触传递的含GluA2R的天然受体的功能。
更新日期:2017-10-20
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