Regulation of dendritic spine morphogenesis by the PDZ domain-containing protein afadin/AF6 and the Rac1-GEF kalirin

Changes in the number and shape of dendritic spines during development and plasticity are important for the formation of neuronal circuits and synaptic plasticity. We previously identified the Rac1-GEF kalirin-7 as a key regulator of spine morphogenesis and showed that kalirin is regulated by EphB2 receptors. We report that the protein afadin/AF6, a component of adherent junctions, and a binding partner of EphB2, is also present in the dendritic spines of cultured hippocampal neurons, where it co-localizes with kalirin. Afadin/AF6 interacts with kalirin in brain and heterologous cells. When over-expressed in neurons, afadin/AF6 is targeted to spines and induces kalirin-dependent spine morphogenesis. We identified structural determinants of afadin/AF6 synaptic targeting and spine morphogenic activity which led us to potential mechanisms for upstream regulation.