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

Biochemistry. 2003 May 20;42(19):5640-8. doi: 10.1021/bi034025x.


Rod outer segment membrane guanylate cyclase (ROS-GC) transduction system is a central component of the Ca(2+)-sensitive phototransduction machinery. The system is composed of two parts: Ca(2+) sensor guanylate cyclase activating protein (GCAP) and ROS-GC. GCAP senses Ca(2+) 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 Ca(2+)-stimulated ROS-GC1 transduction system [Duda, T., et al. (2002) EMBO J. 21, 2547-2556]. In this case, S100beta senses Ca(2+) and stimulates the cyclase. The inhibitory and stimulatory Ca(2+)-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 S100beta modules. GCAP1 senses the Ca(2+) impulse and inhibits the catalytic module; S100beta senses the impulse and stimulates the catalytic module. Thus, ROS-GC1 acts as a bimodal Ca(2+) signal transduction switch in the photoreceptor bipolar synapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Calcium Signaling
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / metabolism
  • Cattle
  • Guanylate Cyclase / chemistry*
  • Guanylate Cyclase / metabolism*
  • Guanylate Cyclase-Activating Proteins
  • In Vitro Techniques
  • Kinetics
  • Models, Molecular
  • Protein Structure, Tertiary
  • Receptors, Cell Surface*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Retinal Cone Photoreceptor Cells / metabolism
  • Rod Cell Outer Segment / metabolism
  • Synapses / metabolism
  • Vision, Ocular


  • Calcium-Binding Proteins
  • Guanylate Cyclase-Activating Proteins
  • Receptors, Cell Surface
  • Recombinant Proteins
  • guanylate cyclase 1
  • Guanylate Cyclase