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

J Biol Chem. 2000 Aug 18;275(33):25061-4. doi: 10.1074/jbc.C000319200.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Brain / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Cloning, Molecular
  • Cytosol / chemistry
  • Glutathione Transferase / metabolism
  • Kinetics
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / chemistry
  • Sialoglycoproteins / metabolism*


  • Lrrc7 protein, mouse
  • Lrrc7 protein, rat
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Sialoglycoproteins
  • Glutathione Transferase
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases

Associated data

  • GENBANK/AF266164