Possible stimulation of retinal rod recovery to dark state by cGMP release from a cGMP phosphodiesterase noncatalytic site.

The Journal of Biological Chemistry
A YamazakiF Hayashi

Abstract

Cyclic GMP phosphodiesterase, a key enzyme for phototransduction, contains alpha, beta (Palphabeta), and two gamma (Pgamma) subunits. In addition to catalytic sites, Palphabeta has two classes of noncatalytic cGMP binding sites with different affinities (Kd values <100 nM and >1 microM). Pgamma regulates Palphabeta as an inhibitor of cGMP hydrolysis and as a stimulator of cGMP binding to the high affinity noncatalytic sites. Pgamma release from Palphabeta by the GTP-bound alpha subunit of transducin (GTP.Talpha) interrupts these two functions. Here we describe a novel regulation of the Pgamma release by [cGMP] and its physiological implication. We isolated Pgamma mutants that exhibit abnormally one of these two functions, indicating the distinct domains in Pgamma are involved to express these functions. When [cGMP] was high ( approximately 5 microM), Pgamma responsible for the inhibition of cGMP hydrolysis was preferentially released, and cGMP hydrolysis activity of Palphabeta was increased about 10 times. When [cGMP] was low (less than approximately 0.5 microM), Pgamma responsible for the stimulation of cGMP binding to the high affinity sites was released. The Pgamma release resulted in the decrease of relative affinity of cGM...Continue Reading

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Citations

Oct 6, 2001·Progress in Retinal and Eye Research·I M Pepe
Feb 14, 1998·The Journal of General Physiology·P D CalvertV Y Arshavsky
Jan 30, 2002·The Journal of General Physiology·Peter D CalvertClint L Makino
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ana RascónJoseph A Beavo
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·S H SoderlingJ A Beavo
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J M HetmanJ A Beavo
Mar 21, 2003·Biochemical and Biophysical Research Communications·Han LiuFumio Hayashi
Jun 23, 1998·The Journal of Biological Chemistry·S H SoderlingJ A Beavo
Sep 12, 1998·The Journal of Biological Chemistry·A E GranovskyN O Artemyev
Jan 12, 2001·Physiological Reviews·G L FainY Koutalos
Jul 17, 2001·Journal of Molecular Biology·J F Kameni TcheudjiP Schultz

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