Isoform-dependent Regulation of Drebrin Dynamics in Dendritic Spines

Dendritic spines have stable filamentous actin (F-actin) and dynamic F-actin. The formation of stable F-actin plays a pivotal role in spine formation. Drebrin binds to and stabilizes F-actin in dendritic spines. Interestingly, the conversion of the drebrin E isoform to drebrin A occurs in parallel with synapse formation, suggesting that this conversion promotes synapse formation via F-actin accumulation. In this study, we measured the dynamics of GFP-tagged drebrin E (GFP-DE) and drebrin A (GFP-DA) in cultured hippocampal neurons by fluorescence recovery after photobleaching analysis. We found that GFP-DA has a larger stable fraction than GFP-DE. The stable drebrin fraction reflects its accumulation in dendritic spines, therefore the isoform conversion may increase the amount of stable F-actin in dendritic spines. The stable fraction was dependent on the drebrin A-specific sequence Ins2, located in the middle of the drebrin protein. In addition, F-actin depolymerization with latrunculin A significantly reduced the stable GFP-DA fraction. These findings indicate that preferential binding of drebrin A to F-actin than drebrin E causes higher stable fraction of drebrin A in dendritic spines, although the F-actin-binding ability of purified drebrin E and drebrin A are comparable. Therefore, we suggest that a drebrin isoform conversion from drebrin E to drebrin A in dendritic spines results in the accumulation of drebrin-bound stable F-actin, which plays a pivotal role in synapse formation. (C) 2018 Published by Elsevier Ltd on behalf of IBRO.