title: Activity-dependent dendritic spine shrinkage and growth involve downregulation of cofilin via distinct mechanisms.
abstract: A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity.
authors.affiliation: Division of Biological Sciences, and Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Calabrese
authors.affiliation: Division of Biological Sciences, and Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Saffin
authors.affiliation: Division of Biological Sciences, and Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Shelley
authors.initials: S
authors.lastname: Halpain
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D054461:Lim Kinases / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D018613:Microscopy, Confocal; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010739:Phospholipase D / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D059008:Time-Lapse Imaging
chemical_list: D000199:Actins; D051338:Cofilin 1; D016202:N-Methylaspartate; D054461:Lim Kinases; D010739:Phospholipase D; C106801:phospholipase D1; D016559:Tacrolimus
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