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Excitatory synapses are located on actin-rich protrusions known as dendritic spines. [alpha]-Actinin is an actin binding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Because it also binds to NMDA receptors and other PSD components, [alpha]-actinin has been proposed to link NMDA receptors and the PSD to the underlying actin cytoskeleton of the dendritic spine. Although [alpha]-actinin has been implicated in modulation of NMDA receptor activity, the cell biological function of [alpha]-actinin in neurons is unknown. We report here that [alpha]-actinin is concentrated in spines. Both the actin binding domain and the spectrin repeat region (which interacts with NMDA receptors) of [alpha]-actinin2 are required for spine targeting. In live imaging experiments, Venus-tagged [alpha]-actinin2 in dendritic spines showed faster turnover than PSD-95, as determined by fluorescent recovery after photobleaching (FRAP), and individual spines often showed marked fluctuations in [alpha]-actinin content over a time-scale of minutes. Overexpression of [alpha]-actinin2 increased the length and density of dendritic protrusions in cultured hippocampal neurons, an effect that requires the actin binding domain and the spectrin repeats of [alpha]-actinin. These results suggest that [alpha]-actinin regulates spine morphology and density.

(C) 2004Elsevier, Inc.