Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Mitochondrial fission and trafficking to dendritic protrusions have been implicated in dendritic spine development. Here, we show that Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1) controls depolarization-induced mitochondrial movement into dendritic spines and filopodia and regulates spine morphogenesis. Depolarization-induced degradation of the p35 regulatory subunit of cyclin-dependent kinase 5 (Cdk5), with the resultant decreased inhibitory phosphorylation on WAVE1, depend on NMDA receptor activation. Thus, WAVE1 dephosphorylation and activation are likely associated with mitochondrial redistribution and spine morphogenesis.