Modulation of phosphodiesterase6 turnoff during background illumination in mouse rod photoreceptors.
In rod photoreceptors of wild-type mice, background light produces an acceleration of the decay of responses to brief flashes, accompanied by a decrease in the rate-limiting time constant for response decay. In rods in which phosphodiesterase gamma (PDEgamma) lacks one of its sites of phosphorylation (T35A rods), both the waveform of response decay and the rate-limiting time constant are nearly unaffected by backgrounds. These effects are not the result of the removal of the phosphorylation site per se, because rods lacking both of the phosphorylation sites of PDEgamma (T22A/T35A rods) adapt to light in a nearly normal manner. Because PDEgamma is one of the proteins of the GTPase activating protein (GAP) complex, our experiments argue for a novel mechanism of photoreceptor light adaptation produced by modulation of GAP-dependent hydrolysis of transducin alpha GTP. In PDEgamma T35A rods, a change in the conformation of the PDEgamma subunit may hinder or mask this mechanism, which in mammals appears to be primarily responsible for the quickening of the temporal resolution of the rod response in backgrounds. Modulation of PDE turnoff also helps to prevent premature saturation of the rod in bright backgrounds, thus making an important contribution to light adaptation. Our experiments provide evidence for modulation of GAP protein-dependent response turnoff, which may also play a role in controlling signal duration at hormone receptors and synapses in the CNS.
Woodruff
Michael L
ML
Department of Physiological Science, University of California Los Angeles, Los Angeles, California 90095-1606, USA.
Janisch
Kerstin M
KM
Peshenko
Igor V
IV
Dizhoor
Alexander M
AM
Tsang
Stephen H
SH
Fain
Gordon L
GL
D000221:Adaptation, Ocular; D000818:Animals; D002118:Calcium / Q000378:metabolism; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000172:deficiency / Q000378:metabolism*; D003623:Dark Adaptation; D004307:Dose-Response Relationship, Radiation; D005071:Evoked Potentials / Q000502:physiology; D008029:Lighting; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000379:methods; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D002118:Calcium