COMPETITIVE-BINDING OF ALPHA-ACTININ AND CALMODULIN TO THE NMDA RECEPTOR

The mechanisms by which neurotransmitter receptors are immobilized at postsynaptic sites in neurons are largely unknown. The activity of NMD A (N-methyl-D-aspartate) receptors is mechano-sensitive(1) and depende nt on the integrity of actin(2), suggesting a functionally important i nteraction between NMDA receptors and the postsynaptic cytoskeleton, a lpha-Actinin-2, a member of the spectrin/dystrophin family of actin-bi nding proteins, is identified here as a brain postsynaptic density pro tein that colocalizes in dendritic spines with NMDA receptors and the putative NMDA receptor-clustering molecule PSD-95, alpha-Actinin-2 bin ds by its central rod domain to the cytoplasmic tail of both NR1 and N R2B subunits of the NMDA receptor, and can be immunoprecipitated with NMDA receptors and PSD-95 from rat brain. Intriguingly, NR1-alpha-acti nin binding is directly antagonized by Ca2+/calmodulin. Thus alpha-act inin may play a role in both the localization of NMDA receptors and th eir modulation by Ca2+.