MOLECULAR CHARACTERIZATION OF S100A1-S100B PROTEIN IN RETINA AND ITS ACTIVATION MECHANISM OF BOVINE PHOTORECEPTOR GUANYLATE-CYCLASE

In contrast to the membrane guanylate cyclases which are stimulated by extracellular ligands, rod outer segment membrane guanylate cyclase ( ROS-GC) activity is modulated intracellularly by calcium in two ways: one, where it is inhibited, and the other, where it is stimulated. The former way is linked to the phototransduction, and physiology of the second is unknown. In both ways calcium modulation of the cyclase occu rs through the calcium binding proteins: through guanylate cyclase act ivating proteins (GCAPs) in the case of phototransduction, and through the recently discovered calcium-dependent GCAP (CD-GCAP) in the case of the other way. The kinase-like domain of ROS-GC is critical for the phototransduction-linked process. The present study shows the express ion of alpha and beta chains of S100Al-S100B protein in the bovine ret ina and demonstrates that this protein stimulates ROS-GC activity in a dose-dependent fashion, that the stimulation is calcium dependent wit h an EC(50) of 17 mu M, and that the kinase-like domain is not involve d in the calcium-modulated cyclase activation. Instead the involved do main resides at the C-terminal segment, between amino acids 731 and 10 54. Thus, this S100Al-S100B protein-mediated calcium-modulated signal transduction mechanism is novel. Furthermore, this study provides the molecular understanding of the two transduction processes mediated by the same ROS-GC, one linked to the low and the other to the high calci um levels.