Activity-dependent dendritic spine shrinkage and growth involve downregulation of cofilin via distinct mechanisms.

Activity-dependent dendritic spine shrinkage and growth involve downregulation of cofilin via distinct mechanisms.
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DOI:
10.1371/journal.pone.0094787
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Halpain S
Halpain S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Calabrese B;Saffin JM;Halpain S

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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.
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