Impaired actin dynamics and suppression of Shank2-mediated spine enlargement in cortactin knockout mice

Abstract

Cortactin regulates actin polymerization and stabilizes branched actin network. In neurons, cortactin is enriched in dendritic spines that contain abundant actin polymers. To explore the function of cortactin in dendritic spines, we examined spine morphology and dynamics in cultured neurons taken from cortactin knockout (KO) mice. Histological analysis revealed that the density and morphology of dendritic spines were not significantly different between wild-type (WT) and cortactin KO neurons. Time-lapse imaging of hippocampal slice cultures showed that the extent of spine volume change was similar between WT and cortactin KO neurons. Despite little effect of cortactin deletion on spine morphology and dynamics, actin turnover in dendritic spines was accelerated in cortactin KO neurons. Furthermore, we detected a suppressive effect of cortactin KO on spine head size under the condition of excessive spine enlargement induced by overexpression of a prominent postsynaptic density protein Shank2. These results suggest that cortactin may have a role in maintaining actin organization by stabilizing actin filaments near the postsynaptic density. Cortactin is an actin-binding protein enriched in the synapse. Neurons without cortactin show accelerated spine actin turnover and reduced ability to increase spine size triggered by overexpression of Shank2, a prominent postsynaptic protein. Cortactin may play a role in actin fi lament maintenance and spine shape regulation in mammalian neurons.