Potential Role of Drebrin A, an F-Actin Binding Protein, in Reactive Synaptic Plasticity after Pilocarpine-Induced Seizures: Functional Implications in Epilepsy
Figure 5
Potential signaling pathways and molecular mechanisms mediating dendritic spine injury and drebrin A loss in epilepsy. Acute seizure or chronic epileptogenesis may lead to activation of calcium-dependent phosphatase, calcineurin, which in turn causes cofilin dephosphorylation either directly or indirectly via an intermediary phosphatase, known as slingshot. Cofilin activity can also be regulated by phosphorylation via the PAK-LIM-kinase pathway. Thus, higher slingshot and/or lower PAK/LIM kinase activities in the hippocampi with epilepsy, leading to less phosphorylation of cofilin, would potentially increase cofilin binding to F-actin, and this could cause depolymerization of F-actin, leading to the prevention and/or dissociation of drebrin from its actin-binding site. This would result in drebrin A translocation to the cytosol leading to its degradation by active caspase. Ultimately, the breakdown of the actin cytoskeleton in dendrites can lead to synaptic dysfunction in epilepsy.
