Effect of photoreceptor degeneration on RNA splicing andexpression of AMPA receptors

[摘要] Purpose: Glutamate is the most important neurotransmitter forexcitatory synapses, and its ionotropicα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)receptor is widely expressed in the vertebrate retina. AMPA receptorsare hetero-oligomers composed of subsets of four distinct subunitstermed GluR1-4. This study was conducted to examine the developmentalprogression of the flip-to-flop alternative splicing switch of AMPAreceptors in wild-type and rd mouse retina.Methods: The flop:flip ratio and expression levels of GluR1-4 frompostnatal day 8 (P8) to P40 were calculated using quantitative real-timepolymerase chain reaction (PCR) analysis and immunoblot analysis. Thetime course of photoreceptor degeneration in rd mice washistologically analyzed.Results: In wild-type mouse retina, the flop:flip ratio in GluR1,but not GluR2-4, dramatically increased between P16 and P20. In rdmice, photoreceptor degeneration progressed from P10 to P20. GluR1flop:flip ratio in rd mice was normal compared with wild-type micebefore P16, however, the dramatic increase between P16 and P20 wascompletely suppressed. The suppression in the later phase of retinaldegeneration was specific to GluR1 and was not observed in GluR2-4.Moreover, the expression levels of GluR1, GluR3, and GluR4 wereincreased in rd mice.Conclusions: These results suggest that the inherited form ofphotoreceptor degeneration in rd mice contributes to the regulationof the flip-to-flop exon switch in GluR1 and the expression levels ofAMPA receptors.

[学科分类] 生物化学/生物物理