S100B serves as a Ca(2+) sensor for ROS-GC1 guanylate cyclase in cones but not in rods of the murine retina

Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca(2+) signal transduction switch. Lowering Ca(2+)](i) from 200 to 20 nM progressively turns it "ON" as does raising Ca(2+)](i) from 500 to 5000 nM. The mode operating at lower Ca(2+)](i) plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated Ca(2+)](i) is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca(2+)-sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K(1/2) for Ca(2+) greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where Ca(2+)](i) levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in Ca(2+)](i) in cone outer segments. The findings define a new cone-specific Ca(2+)-dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.