Effect of photoreceptor degeneration on RNA splicing and expression of AMPA receptors.
OBJECTIVE
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.
Namekata
Kazuhiko
K
Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan.
Okumura
Akinori
A
Harada
Chikako
C
Nakamura
Kazuaki
K
Yoshida
Hiroshi
H
Harada
Takayuki
T
D000375:Aging / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D014644:Genetic Variation; D051379:Mice; D008817:Mice, Mutant Strains; D012326:RNA Splicing; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2