Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation

Discs large (DLG) mediates the clustering of synaptic molecules. Here we de monstrate that synaptic localization of DLG itself is regulated by CaMKII. We show that DLG and CaMKII colocalize at synapses and exist in the same pr otein complex. Constitutively activated CaMKII phenocopied structural abnor malities of dig mutant synapses and dramatically increased extra-junctional DLG. Decreased CaMKII activity caused opposite alterations. In vitro, CaMK II phosphorylated a DLG fragment with a stoichiometry close to one. Moreove r, expression of site-directed dig mutants that blocked or mimicked phospho rylation had effects similar to those observed upon inhibiting or constitut ively activating CaMKII. We propose that CaMKII-dependent DLG phosphorylati on regulates the association of DLG with the synaptic complex during develo pment and plasticity, thus providing a link between synaptic activity and s tructure.