Association of calcium/calmodulin-dependent kinase II with developmentally regulated splice variants of the postsynaptic density protein densin-180.
In a continuing search for proteins that target calcium/calmodulin-dependent protein kinase II (CaMKII) to postsynaptic density (PSD) substrates important in synaptic plasticity, we showed that the PSD protein densin-180 binds CaMKII. Four putative splice variants (A-D) of the cytosolic tail of densin-180 are shown to be differentially expressed during brain development. Densin-180 splicing affects CaMKII phosphorylation of specific serine residues. Variants A, B, and D, but not C, bind CaMKII stoichiometrically and with high affinity, mediated by a differentially spliced domain. Densin-180 differs from the previously identified CaMKII-binding protein NR2B in that binding does not strictly require CaMKII autophosphorylation. Binding of densin-180 and NR2B to CaMKII is noncompetitive, indicating different interaction sites on CaMKII. Expression of the membrane-targeted CaMKII-binding domain of densin-180 confers membrane localization to coexpressed CaMKII without requiring calcium mobilization, suggesting that densin-180 plays a role in the constitutive association of CaMKII with PSDs.
Strack
S
S
Department of Molecular Physiology and Biophysics and Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA.
Robison
A J
AJ
Bass
M A
MA
Colbran
R J
RJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D003600:Cytosol / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism*
C504462:Lrrc7 protein, mouse; C504463:Lrrc7 protein, rat; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; D005982:Glutathione Transferase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases