Calcium-modulated guanylate cyclase transduction machinery in the photoreceptor-bipolar synaptic region

Rod outer segment membrane guanylate cyclase (ROS-GC) transduction system is a central component of the Ca²⁺-sensitive phototransduction machinery. The system is composed of two parts: Ca²⁺ sensor guanylate cyclase activating protein (GCAP) and ROS-GC. GCAP senses Ca²⁺ impulses and inhibits the cyclase. This operational feature of the cyclase is considered to be unique and exclusive in the phototransduction machinery. A combination of reconstitution, peptide competition, cross-linking, and immunocytochemical studies has been used in this study to show that the GCAP1/ROS-GC1 transduction system also exists in the photoreceptor synaptic (presynaptic) termini. Thus, the presence of this system and its linkage is not unique to the phototransduction machinery. A recent study has demonstrated that the photoreceptor-bipolar synaptic region also contains a Ca²⁺-stimulated ROS-GC1 transduction system [Duda, T., et al. (2002) EMBO J. 21, 2547-2556]. In this case, S100β senses Ca²⁺ and stimulates the cyclase. The inhibitory and stimulatory Ca²⁺-modulated ROS-GC1 sites are distinct. These findings allow the formation of a new topographic model of ROS-GC1 transduction. In this model, the catalytic module of ROS-GC1 at its opposite ends is flanked by GCAP1 and S100β modules. GCAP1 senses the Ca²⁺ impulse and inhibits the catalytic module; S100β senses the impulse and stimulates the catalytic module. Thus, ROS-GC1 acts as a bimodal Ca²⁺ signal transduction switch in the photoreceptor bipolar synapse.