Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin

Abstract

DURING light-adaptation by the vertebrate eye, the rods are desensitized and the light response is accelerated^1,2. When light is absorbed by the rods, a phosphodiesterase is activated that hydrolyses cyclic GMP^3,4. A light-induced decrease in cytoplasmic Ca²⁺ concentration^5–7 is part of this light-adaptation process^8,9. 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 µM; 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 ˜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.