ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors.
Cholera toxin and pertussis toxin catalyze ADP-ribosylation of the alpha-subunits of the GTP-binding stimulatory (Ns) and inhibitory (Ni) coupling components, respectively, of adenylate cyclase. Cholera toxin also catalyzes the ADP-ribosylation of transducin, the GTP-binding signal-coupling protein of retinal rod outer segments, and thereby reduces its light-stimulated GTPase activity. We show here that pertussis toxin also ADP-ribosylates transducin. Illumination markedly inhibits the ADP-ribosylation of transducin by pertussis toxin. ADP-ribosylation by this toxin in the dark is also lessened by prior incubation with hydrolysis-resistant GTP analogs. These inhibitory effects indicate that the GDP complex of transducin is the preferred form for ADP-ribosylation by pertussis toxin. Transducin modified by this toxin has a lower affinity for photoexcited rhodopsin than does unmodified transducin. ADP-ribosylation inhibits the light-stimulated GTPase activity of rod outer segments and blocks the signal-coupling activity of transducin in photoactivation of the phosphodiesterase. These and previous results show that cholera and pertussis toxins preferentially ADP-ribosylate the active (GTP-binding) and inactive (GDP-binding) conformations, respectively, of transducin. Correspondingly, ADP-ribosylation by these toxins inhibits GTPase activity by stabilizing transducin in the preferred active (GTP-binding) or inactive (GDP-binding) conformation. The actions of pertussis toxin on retinal rod outer segments provide further evidence for a high degree of homology between retinal transducin and the N proteins of the adenylate cyclase system.
D037361:Adenylate Cyclase Toxin; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D037342:Pertussis Toxin; D010782:Photolysis; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000187:drug effects* / Q000378:metabolism; D015293:Transducin; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D001427:Bacterial Toxins; D008565:Membrane Proteins; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D015293:Transducin; D006152:Cyclic GMP