GAP-independent termination of photoreceptor light response by excess gamma subunit of the cGMP-phosphodiesterase.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Steven H TsangGordon L Fain

Abstract

We have generated a mouse with rod photoreceptors overexpressing the gamma inhibitory subunit (PDE6gamma) of the photoreceptor G-protein effector cGMP phosphodiesterase (PDE6). PDE6gamma overexpression decreases the rate of rise of the rod response at dim intensities, indicating a reduction in the gain of transduction that may be the result of cytoplasmic PDE6gamma binding to activated transducin alpha GTP (Talpha-GTP) before the Talpha-GTP binds to endogenous PDE6gamma. Excess PDE6gamma also produces a marked acceleration in the falling phase of the light response and more rapid recovery of sensitivity and circulating current after prolonged light exposure. These effects are not mediated by accelerating GTP hydrolysis through the GAP (GTPase activating protein) complex, because the decay of the light response is also accelerated in rods that overexpress PDE6gamma but lack RGS9. Our results show that the PDE6gamma binding sites of PDE6 alpha and beta are accessible to excess (presumably cytoplasmic) PDE6gamma in the light, once endogenous PDE6gamma has been displaced from its binding site by Talpha-GTP. They also suggest that in the presence of Talpha-GTP, the PDE6gamma remains attached to the rest of the PDE6 molecule, but aft...Continue Reading

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Citations

Jan 18, 2007·Pflügers Archiv : European journal of physiology·Yingbin Fu, King-Wai Yau
Jan 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jikui SongJohn L Markley
May 1, 2010·Physiology·Marie E Burns, Edward N Pugh
Jul 29, 2008·Investigative Ophthalmology & Visual Science·Richard J DavisStephen H Tsang
Jun 3, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander V KolesnikovOleg G Kisselev
Nov 9, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ching-Kang ChenGordon L Fain
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