Drebrin Is A Leaky Capper Of Actin Filaments Modulating The Effects Of Formins

Drebrin A is neuronal F-actin-binding protein enriched in dendritic spines, which are playing a major role in synaptic plasticity. Molecular cross-talk between drebrin and key neuronal actin-binding proteins is believed to be a part of the cytoskeleton-modulating pathway that is implicated also in synaptic dysfunction in Alzheimer's disease (AD), Down syndrome, epilepsy and normal aging. However, drebrin effects on actin dynamics and its interplay with main neuronal ABPs (such as severing proteins, cappers, elongation factors) are yet to be clarified. Here, we show that drebrin A is a leaky capper of actin filaments. Solution assays monitoring pyrene fluorescence of actin indicate that drebrin affects barbed- but not pointed end polymerization. Real time TIRF assays revealed >2-fold inhibition of F-actin elongation rate by drebrin A. Such inhibition was observed also in the presence of profilin. Moreover, consistent with its capping activity, drebrin inhibits F-actin annealing. These results called for examination of drebrin effects on barbed end binding factors, such as formins. Pyrene fluorescence assays show inhibition of formin-induced actin polymerization by drebrin A in the presence of profilin. The mechanism of such inhibition and its biological implications will be discussed.