CO₂/bicarbonate modulates cone photoreceptor ROS-GC1 and restores its CORD6-linked catalytic activity.

ABSTRACT: This study with recombinant reconstituted system mimicking the cellular conditions of the native cones documents that photoreceptor ROS-GC1 is modulated by gaseous CO₂. Mechanistically, CO₂ is sensed by carbonic anhydrase (CAII), generates bicarbonate that, in turn, directly targets the core catalytic domain of ROS-GC1, and activates it to increased synthesis of cyclic GMP. This, then, functions as a second messenger for the cone phototransduction. The study demonstrates that, in contrast to the Ca²⁺-modulated phototransduction, the CO₂ pathway is Ca²⁺-independent, yet is linked with it and synergizes it. It, through R⁷⁸⁷C mutation in the third heptad of the signal helix domain of ROS-GC1, affects cone-rod dystrophy, CORD6.

SUBMITTER: Duda T 

PROVIDER: S-EPMC6687076 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature