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通过核RNA编辑控制AMPA受体通道的动力学特性

Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.

作者信息

Lomeli H, Mosbacher J, Melcher T, Höger T, Geiger J R, Kuner T, Monyer H, Higuchi M, Bach A, Seeburg P H

机构信息

Laboratory of Molecular Neuroendocrinology, University of Heidelberg, Germany.

出版信息

Science. 1994 Dec 9;266(5191):1709-13. doi: 10.1126/science.7992055.

Abstract

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor channels mediate the fast component of excitatory postsynaptic currents in the central nervous system. Site-selective nuclear RNA editing controls the calcium permeability of these channels, and RNA editing at a second site is shown here to affect the kinetic aspects of these channels in rat brain. In three of the four AMPA receptor subunits (GluR-B, -C, and -D), intronic elements determine a codon switch (AGA, arginine, to GGA, glycine) in the primary transcripts in a position termed the R/G site, which immediately precedes the alternatively spliced modules "flip" and "flop." The extent of editing at this site progresses with brain development in a manner specific for subunit and splice form, and edited channels possess faster recovery rates from desensitization.

摘要

AMPA(α-氨基-3-羟基-5-甲基-4-异恶唑丙酸)受体通道介导中枢神经系统中兴奋性突触后电流的快速成分。位点选择性核RNA编辑控制这些通道的钙通透性,本文显示第二个位点的RNA编辑会影响大鼠脑中这些通道的动力学方面。在四个AMPA受体亚基(GluR-B、-C和-D)中的三个中,内含子元件在一个称为R/G位点的位置决定初级转录本中的密码子转换(AGA,精氨酸,变为GGA,甘氨酸),该位点紧接在可变剪接模块“翻转”和“摆动”之前。该位点的编辑程度随脑发育而进展,其方式因亚基和剪接形式而异,且编辑后的通道脱敏恢复速率更快。

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