ROS-GC interlocked Ca(2+)-sensor S100B protein signaling in cone photoreceptors: review.
Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to visual transduction; it generates cyclic GMP, the second messenger of the photon signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic GMP, typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes with guanylate cyclase activating proteins (GCAPs), which are Ca(2+)-sensing elements. There is a light-induced fall in intracellular Ca(2+). As Ca(2+) dissociates from GCAPs in the 20-200 nM range, ROS-GC activity rises to quicken the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as Ca(2+) and cyclic GMP levels return to baseline. To date, GCAPs mediate the only known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian cone outer segments, cone synapses and ON bipolar cells, another Ca(2+) sensor protein, S100B, complexes with ROS-GC1 and senses the Ca(2+) signal with a K1/2 of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca(2+) is bound. Thus, the ROS-GC system in cones functions as a Ca(2+) bimodal switch; with rising intracellular Ca(2+), its activity is first turned down by GCAPs and then turned up by S100B. This presentation provides a historical perspective on the role of S100B in the photoreceptors, offers a pictorial model for the "bimodal" operation of the ROS-GC switch and projects future tasks that are needed to understand its operation. Some accounts of this review have been adopted from the original publications of these authors.
Research Divisions of Biochemistry and Molecular Biology, The Unit of Regulatory and Molecular Biology, Salus University Elkins Park, PA, USA.
Rameshwar K
RK
Sharma
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Boston, MA, USA.
Clint L
CL
Makino
Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neuroscience, CNRS UPR 3212 Strasbourg, France.
David
D
Hicks
Research Divisions of Biochemistry and Molecular Biology, The Unit of Regulatory and Molecular Biology, Salus University Elkins Park, PA, USA.
Teresa
T
Duda
ROS-GC guanylate cyclase; S100B; cones; cyclic GMP; phototransduction