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As the eye flicks about a scene, a photoreceptor, rod and cone, sees an alternating pattern of light and dark. This pattern
is transduced by the photoreceptor outer segment into electrical signals (a mechanism termed phototransduction), and
these signals are processed first by the retina, then by the visual cortex, and finally are decoded as the perceived image. In the
phototransduction cascade of rods and cones, the second messenger cyclic GMP is generated by membrane-bound guanylate
cyclases (ROS-GCs). In darkness, cyclic GMP opens cyclic nucleotide-gated (CNG) channels and a steady influx of Na+ and
Ca2+ enters the outer segment and keeps the photoreceptor depolarized. Photons trigger hydrolysis of cyclic GMP, closing the
channels and hyperpolarizing the photoreceptor. The recovery phase occurs when the Na+/Ca2+ and K+ exchanger reduces
intracellular concentration of Ca2+. Guanylate cyclase-activating proteins (GCAPs) sense this fall and stimulate ROS-GCs to
synthesize cyclic GMP at a faster rate, leading to recovery of the photoreceptor dark current. The basic phototransduction
components of rods and cones are similar, but important differences render rods more sensitive and cones faster with a larger
dynamic range. While rods express ROS-GC1, ROS-GC2, GCAP1, and GCAP2, cones express only ROS-GC1 and GCAP1.
We have discovered that cone photoreceptors, but not rods, express another Ca2+ sensor, S100B. This protein stimulates cyclic
GMP synthesis as intracellular concentration of Ca2+ increases, and this modulation is specific to ROS-GC1, the only guanylate
cyclase expressed in cones. Thus, ROS-GC1 functions as a Ca2+-bimodal switch that increases its rate of cyclic GMP synthesis
when intracellular Ca2+ rises to higher levels or falls to very low levels. We hypothesized that this bimodal feature serves cone
function to better operate during daytime when cones are continuously light adapted and their function is to convey both
light increments and decrements. While GCAP unimodal modulation of ROS-GC1 in rods provides negative feedback and
is responsible primarily for accelerating response recovery, the GCAP/S100B bimodal feature can provide both negative and
positive feedback, accelerating both the recovery and the rising phases.
Teresa Duda has received her PhD from Adam Mickiewicz University Poznan, Poland. In 1987, she joined Dr. Sharma’s research group at the University of Tennessee, Memphis as a Post-doctoral Fellow and started her work on Membrane Guanylate Cyclase Signal Transduction. She is now a Professor at Salus University USA and continues to study various aspects of Membrane Guanylate Cyclase Signaling. She has published more than 90 papers in high-input journals and has been serving as an Editorial Board Member of Frontiers in Molecular Neuroscience.