Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons

Nature. 1994 Apr 28;368(6474):853-6. doi: 10.1038/368853a0.


Phosphorylation of molecules involved in synaptic transmission by multifunctional protein kinases modulates both pre- and post-synaptic events in the central nervous system. The positioning of kinases near their substrates may be an important part of the regulatory mechanism. The A-kinase-anchoring proteins (AKAPs; ref. 3) are known to bind the regulatory subunit of cyclic AMP-dependent protein kinase A with nanomolar affinity. Here we show that anchoring of protein kinase A by AKAPs is required for the modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate channels. Intracellular perfusion of cultured hippocampal neurons with peptides derived from the conserved kinase binding region of AKAPs prevented the protein kinase A-mediated regulation of AMPA/kainate currents as well as fast excitatory synaptic currents. This effect could be overcome by adding the purified catalytic subunit of protein kinase. A control peptide lacking kinase-binding activity had no effect. To our knowledge, these results provide the first evidence that anchoring of protein kinase A is crucial in the regulation of synaptic function.

Publication types

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

MeSH terms

  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Carrier Proteins*
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Humans
  • Membrane Potentials
  • Neurons / metabolism*
  • Peptide Fragments / pharmacology
  • Phosphorylation
  • Proteins / metabolism*
  • Rats
  • Receptors, AMPA / metabolism*
  • Receptors, Kainic Acid / metabolism*
  • Synapses / physiology


  • A Kinase Anchor Proteins
  • AKAP5 protein, human
  • Adaptor Proteins, Signal Transducing
  • Akap5 protein, rat
  • Carrier Proteins
  • Peptide Fragments
  • Proteins
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases