Effect of photoreceptor degeneration on RNA splicing and expression of AMPA receptors.
Effect of photoreceptor degeneration on RNA splicing and expression of AMPA receptors.
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发表时间：
2006-12
期刊：
影响因子：
2.2
通讯作者：
K. Namekata;A. Okumura;C. Harada;Kazuaki Nakamura;H. Yoshida;T. Harada
中科院分区：
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作者：
K. Namekata;A. Okumura;C. Harada;Kazuaki Nakamura;H. Yoshida;T. Harada
谷氨酸是兴奋性突触最重要的神经递质，其嗜离子性α -氨基-3-羟基-5-甲基-4-异唑丙酸受体在脊椎动物视网膜中广泛表达。AMPA受体是由四种不同亚基GluR1-4组成的异聚物。本研究旨在研究野生型和rd小鼠视网膜中AMPA受体的翻转到翻转交替剪接开关的发育过程。方法采用实时荧光定量聚合酶链反应（PCR）和免疫印迹（immunoblot）方法，计算出生后第8天（P8）至第40天GluR1-4的翻翻率和表达水平。组织学分析了rd小鼠光感受器变性的时间过程。结果在野生型小鼠视网膜中，在P16和P20之间，GluR1的翻翻比显著增加，而GluR2-4的翻翻比没有显著增加。在rd小鼠中，光感受器退化从P10进展到P20。在P16出现之前，rd小鼠的GluR1翻翻率与野生型小鼠比较正常，但P16和P20之间的急剧增加被完全抑制。视网膜变性后期的抑制作用仅针对GluR1，而在GluR2-4中未发现。此外，GluR1、GluR3和GluR4在rd小鼠中的表达水平升高。结论：rd小鼠光感受器变性的遗传形式参与调控GluR1的翻转-翻翻外显子开关和AMPA受体的表达水平。
PURPOSE Glutamate is the most important neurotransmitter for excitatory synapses, and its ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is widely expressed in the vertebrate retina. AMPA receptors are hetero-oligomers composed of subsets of four distinct subunits termed GluR1-4. This study was conducted to examine the developmental progression of the flip-to-flop alternative splicing switch of AMPA receptors in wild-type and rd mouse retina. METHODS The flop:flip ratio and expression levels of GluR1-4 from postnatal day 8 (P8) to P40 were calculated using quantitative real-time polymerase chain reaction (PCR) analysis and immunoblot analysis. The time course of photoreceptor degeneration in rd mice was histologically analyzed. RESULTS In wild-type mouse retina, the flop:flip ratio in GluR1, but not GluR2-4, dramatically increased between P16 and P20. In rd mice, photoreceptor degeneration progressed from P10 to P20. GluR1 flop:flip ratio in rd mice was normal compared with wild-type mice before P16, however, the dramatic increase between P16 and P20 was completely suppressed. The suppression in the later phase of retinal degeneration was specific to GluR1 and was not observed in GluR2-4. Moreover, the expression levels of GluR1, GluR3, and GluR4 were increased in rd mice. CONCLUSIONS These results suggest that the inherited form of photoreceptor degeneration in rd mice contributes to the regulation of the flip-to-flop exon switch in GluR1 and the expression levels of AMPA receptors.