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

Autoři: Anna Kruyer aff001;  Lauren E. Ball aff002;  Danyelle M. Townsend aff003;  Peter W. Kalivas aff001;  Joachim D. Uys aff002
Působiště autorů: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, United States of America aff001;  Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States of America aff002;  Department of Drug Discovery and Pharmaceutical Sciences, Medical University of South Carolina, Charleston, SC, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
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.

Klíčová slova:

Cocaine – Cysteine – Database searching – Glutathione – Neuronal dendrites – Nucleus accumbens – Oxidation-reduction reactions – Actins


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