RHODOPSIN PHOSPHORYLATION AS A MECHANISM OF CYCLIC-GMP PHOSPHODIESTERASE REGULATION BY S-MODULIN

DURING light-adaptation by the vertebrate eye, the rods are desensitized and the light response is accelerated1,2. When light is absorbed by the rods, a phosphodiesterase is activated that hydrolyses cyclic GMP3,4. A light-induced decrease in cytoplasmic Ca2+ concentration5-7 is part of this light-adaptation process8,9. The protein S-modulin (M(r) 26,000) is known to increase the fraction of light-activated cyclic GMP-phosphodiesterase (PDE) at high Ca2+ concentrations in frog rod photoreceptors10. Here I present evidence that S-modulin lengthens the lifetime of active PDE (PDE*) at high Ca2+ Concentrations. These S-modulin effects are observed in the physiological range of Ca2+ concentration (30 nM to 1 muM; half-maximum effects at 200-400 nM). At the high Ca2+ concentrations at which S-modulin prolongs the lifetime of PDE*, S-modulin inhibits rhodopsin phosphorylation (half-maximum effect at approximately 100 nM Ca2+). ATP is necessary for the S-modulin effects on PDE activation. I therefore conclude that the Ca2+-dependent regulation of PDE by S-modulin is mediated by rhodopsin phosphorylation. This regulation seems to be the principal mechanism of light adaptation in vertebrate photoreceptors.