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Front Mol Neurosci. 2014 Mar 26;7:21. doi: 10.3389/fnmol.2014.00021. eCollection 2014.

ROS-GC interlocked Ca(2+)-sensor S100B protein signaling in cone photoreceptors: review.

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1
Research Divisions of Biochemistry and Molecular Biology, The Unit of Regulatory and Molecular Biology, Salus University Elkins Park, PA, USA.
2
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School Boston, MA, USA.
3
Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neuroscience, CNRS UPR 3212 Strasbourg, France.

Abstract

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.

KEYWORDS:

ROS-GC guanylate cyclase; S100B; cones; cyclic GMP; phototransduction

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