Post-translational S-glutathionylation of cofilin increases actin cycling during cocaine seeking

• Published in: PloS one 2019-09, Vol.14 (9), p.e0223037
• Main Authors: Kruyer, Anna, Ball, Lauren E, Townsend, Danyelle M, Kalivas, Peter W, Uys, Joachim D
• Format: Article
• Language: English
• Subjects: Actin; Actin Depolymerizing Factors - metabolism; Actins - metabolism; Amino acids; Animal tissues; Animals; Authorship; Behavior, Animal - physiology; Biology and Life Sciences; Cocaine; Cocaine - administration & dosage; Cofilin; Conditioning; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Cues; Cycles; Depolymerization; Drug-Seeking Behavior - physiology; Drugs and athletes; Extinction; Extinction behavior; Food; Glutathione; Glutathione - metabolism; Intracellular signalling; Male; Medicine and Health Sciences; Models, Animal; Muscle proteins; Neurons; Neurosciences; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - physiology; Oxidation; Oxidation-Reduction - drug effects; Oxidation-reduction reactions; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Phosphorylation; Physical Sciences; Post-translation; Protein binding; Protein Processing, Post-Translational - drug effects; Protein Processing, Post-Translational - physiology; Protein S; Proteins; Rats; Research and Analysis Methods; Rodents; Self Administration - psychology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223037

Neuronal defense against oxidative damage is mediated primarily by the glutathione redox system. Traditionally considered a mechanism to protect proteins from irreversible oxidation, mounting evidence supports a role for protein S-glutathionylation in cell signaling in response to changes in intracellular redox status. Here we determined the specific sites on the actin binding protein cofilin that undergo S-glutathionylation. In addition, we show that S-glutathionylation of cofilin reduces its capacity to depolymerize F-actin. We further describe an assay to determine the S-glutathionylation of target proteins in brain tissue from behaving rodents. Using this technique, we show that cofilin in the rat nucleus accumbens undergoes S-glutathionylation during 15-minutes of cued cocaine seeking in the absence of cocaine. Our findings demonstrate that cofilin S-glutathionylation is increased in response to cocaine-associated cues and that increased cofilin S-glutathionylation reduces cofilin-dependent depolymerization of F-actin. Thus, S-glutathionylation of cofilin may serve to regulate actin cycling in response to drug-conditioned cues.