Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation.
Discs large (DLG) mediates the clustering of synaptic molecules. Here we demonstrate that synaptic localization of DLG itself is regulated by CaMKII. We show that DLG and CaMKII colocalize at synapses and exist in the same protein complex. Constitutively activated CaMKII phenocopied structural abnormalities of dlg mutant synapses and dramatically increased extrajunctional DLG. Decreased CaMKII activity caused opposite alterations. In vitro, CaMKII phosphorylated a DLG fragment with a stoichiometry close to one. Moreover, expression of site-directed dlg mutants that blocked or mimicked phosphorylation had effects similar to those observed upon inhibiting or constitutively activating CaMKII. We propose that CaMKII-dependent DLG phosphorylation regulates the association of DLG with the synaptic complex during development and plasticity, thus providing a link between synaptic activity and structure.
Koh
Y H
YH
Department of Biology, University of Massachusetts, Amherst 01003, USA.
Popova
E
E
Thomas
U
U
Griffith
L C
LC
Budnik
V
V
D000818:Animals; D030801:Animals, Genetically Modified; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D016147:Genes, Tumor Suppressor; D005838:Genotype; D049452:Green Fluorescent Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins
D029721:Drosophila Proteins; D019476:Insect Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila; D049452:Green Fluorescent Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases