Association of calcium/calmodulin-dependent kinase II with developmentallyregulated splice variants of the postsynaptic density protein densin-180

In a continuing search for proteins that target calcium/calmodulin-dependen t protein kinase II (CaMKII) to postsynaptic density (PSD) substrates impor tant in synaptic plasticity, we showed that the PSD protein densin-180 bind s CaMKII, Four putative splice variants (A-D) of the cytosolic tail of dens in-180 are shown to be differentially expressed during brain development. D ensin-180 splicing affects CaMKII phosphorylation of specific serine residu es. Variants A, B, and D, but not C, bind CaMKII stoichiometrically and wit h high affinity, mediated by a differentially spliced domain. Densin-180 di ffers from the previously identified CaMKII-binding protein NR2B in that bi nding does not strictly require CaMKII autophosphorylation. Binding of dens in-180 and NR2B to CaMKII is noncompetitive, indicating different interacti on sites on CaMKII. Expression of the membrane-targeted CaMKII-binding doma in of densin-180 confers membrane localization to coexpressed CaMKII withou t requiring calcium mobilization, suggesting that densin-180 plays a role i n the constitutive association of CaMKII with PSDs.