Activity-Dependent Redistribution and Essential Role of Cortactin in Dendritic Spine Morphogenesis

The number and shape of dendritic spines are influenced by activity and regulated by molecules that organize the actin cytoskeleton of spines. Cortactin is an F-actin binding protein and activator of the Arp2/3 actin nucleation machinery that also interacts with the postsynaptic density (PSD) protein Shank. Cortactin is concentrated in dendritic spines of cultured hippocampal neurons, and the N-terminal half of the protein containing the Arp2/3 and F-actin binding domains is necessary and sufficient for spine targeting. Knockdown of cortactin protein by short-interfering RNA (siRNA) results in depletion of dendritic spines in hippocampal neurons, whereas overexpression of cortactin causes elongation of spines. In response to synaptic stimulation and NMDA receptor activation, cortactin redistributes rapidly from spines to dendritic shaft, correlating with remodeling of the actin cytoskeleton, implicating cortactin in the activity-dependent regulation of spine morphogenesis.