RNA editing of the GABA(A) receptor alpha3 subunit alters the functional properties of recombinant receptors.
RNA editing of the GABA(A) receptor alpha3 subunit alters the functional properties of recombinant receptors.
复制标题
DOI：
10.1016/j.neures.2009.01.003
复制
发表时间：
2009-04
影响因子：
2.9
通讯作者：
Fisher JL
中科院分区：
文献类型：
--
作者：
Nimmich ML;Heidelberg LS;Fisher JL
RNA编辑提供了一种转录后机制来增加基因产物的结构异质性。最近，GABAA受体的α3亚基已被证明可以进行RNA编辑。结果，第三跨膜结构域中高度保守的异亮氨酸残基被甲硫氨酸取代。为了确定这种结构变化对受体功能的影响，我们比较了含有编辑或未编辑形式的α3亚基沿着β3和γ2L的重组受体的GABA敏感性、药理学性质和宏观动力学。编辑大大改变了受体的GABA敏感性和失活率，未编辑的形式显示出较低的GABA EC 50和较慢的衰减。在α1亚基同源位置的突变中观察到类似的效应，表明该位点在通道门控调节中具有共同作用。除了对GABA的反应外，受体的药理学性质不受编辑的影响，各种调节剂也有类似的增强作用。由于α3亚基的RNA编辑在发育过程中增加，我们的研究结果表明，GABA能神经传递可能在发育早期更有效，未编辑的α3亚基具有更高的GABA敏感性和更慢的衰减速率。
RNA editing provides a post-transcriptional mechanism to increase structural heterogeneity of gene products. Recently, the α3 subunit of the GABAA receptors has been shown to undergo RNA editing. As a result, a highly conserved isoleucine residue in the third transmembrane domain is replaced with a methionine. To determine the effect of this structural change on receptor function, we compared the GABA sensitivity, pharmacological properties and macroscopic kinetics of recombinant receptors containing either the edited or unedited forms of the α3 subunit along with β3 and γ2L. Editing substantially altered the GABA sensitivity and deactivation rate of the receptors, with the unedited form showing a lower GABA EC50 and slower decay. Comparable effects were observed with a mutation at the homologous location in the α1 subunit, suggesting a common role for this site in regulation of channel gating. Except for the response to GABA, the pharmacological properties of the receptor were unaffected by editing, with similar enhancement by a variety of modulators. Since RNA editing of the α3 subunit increases through development, our findings suggest that GABAergic neurotransmission may be more effective early in development, with greater GABA sensitivity and slower decay rates conferred by the unedited α3 subunit.
登录
查看更多内容
影响因子：
56.9
作者：
BRUSA, R;ZIMMERMANN, F;SPRENGEL, R
通讯作者：
SPRENGEL, R
影响因子：
56.9
作者：
Hoopengardner, B;Bhalla, T;Reenan, R
通讯作者：
Reenan, R
影响因子：
16.2
作者：
JONES, MV;WESTBROOK, GL
通讯作者：
WESTBROOK, GL
影响因子：
1.7
作者：
Es-Salah, Zeineb;Lapied, Bruno;Hamon, Alain
通讯作者：
Hamon, Alain
影响因子：
4.8
作者：
Böhme, I;Rabe, H;Lüddens, H
通讯作者：
Lüddens, H