Physical and functional interactions of cyclophilin B with neuronal actin and peroxiredoxin-1 are modified by oxidative stress.
Presynaptic actin was identified as a new Torpedo cyclophilin B partner captured in pull-down experiments and by coimmunoprecipitation. The cyclophilin B-actin pull-down interaction was insensitive to the blockade of peptidyl cis/trans prolyl isomerase and calcineurin activities and to the latrunculin A- and jasplakinolide-mediated perturbation of F-actin polymerization. Conversely, it was reduced by ATP and stimulated by a low Cu(2+) treatment of synaptosomes and by acrolydan-conjugated cyclophilin B. This Cu(2+)-induced stress, in parallel, stimulates the formation of GSH adducts with cysteines of synaptosomal actin followed by its deglutathionylation and its dimerization in the presence of higher Cu(2+) concentrations. The reversibility of the thiol processing of actin occurred in the same range of Cu(2+) concentrations that mediated a stronger cyclophilin B-actin interaction, suggesting cyclophilin B participation in antioxidant processes. Among 2-Cys-peroxiredoxin isoforms, mainly peroxiredoxin-1 was found in cell bodies and nerve endings. Functionally, both Torpedo and human peroxiredoxin-1 were activated in vitro by Torpedo cyclophilin B. Moreover, cyclophilin B, like thioredoxins, maintained an H(2)O(2)-dependent peroxidase activity of peroxiredoxin-1 in the presence of dithiothreitol. Thus, the monocysteinic Torpedo cyclophilin B is able to sustain peroxiredoxin-1 activity and might be involved in the presynaptic defense against oxidative stress affecting G-actin posttranslational changes and its redox signaling in nerve ending compartments.
Morot-Gaudry-Talarmain
Yvette
Y
Laboratoire de Neurobiologie Cellulaire et Moléculaire-UPR9040, CNRS, Institut de Neurobiologie Alfred Fessard-FRC2118, Gif sur Yvette, F-91198, France. morot@nbcm.cnrs-gif.fr
D000199:Actins / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000378:metabolism; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014101:Torpedo / Q000378:metabolism*
D000199:Actins; C081786:cyclophilin B; D003300:Copper; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D021983:Cyclophilins