AKAP-anchored PKA maintains neuronal L-type calcium channel activity and NFAT transcriptional signaling

Cell Rep. 2014 Jun 12;7(5):1577-1588. doi: 10.1016/j.celrep.2014.04.027. Epub 2014 May 15.


L-type voltage-gated Ca2+ channels (LTCC) couple neuronal excitation to gene transcription. LTCC activity is elevated by the cyclic AMP (cAMP)-dependent protein kinase (PKA) and depressed by the Ca2+-dependent phosphatase calcineurin (CaN), and both enzymes are localized to the channel by A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 anchoring of CaN also promotes LTCC activation of transcription through dephosphorylation of the nuclear factor of activated T cells (NFAT). We report here that the basal activity of AKAP79/150-anchored PKA maintains neuronal LTCC coupling to CaN-NFAT signaling by preserving LTCC phosphorylation in opposition to anchored CaN. Genetic disruption of AKAP-PKA anchoring promoted redistribution of the kinase out of postsynaptic dendritic spines, profound decreases in LTCC phosphorylation and Ca2+ influx, and impaired NFAT movement to the nucleus and activation of transcription. Thus, LTCC-NFAT transcriptional signaling in neurons requires precise organization and balancing of PKA and CaN activities in the channel nanoenvironment, which is only made possible by AKAP79/150 scaffolding.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A Kinase Anchor Proteins / metabolism*
  • Animals
  • Calcineurin / metabolism
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dendritic Spines / metabolism*
  • Dendritic Spines / physiology
  • HEK293 Cells
  • Humans
  • Mice
  • NFATC Transcription Factors / metabolism*
  • Protein Binding
  • Rats
  • Signal Transduction*
  • Transcriptional Activation*


  • A Kinase Anchor Proteins
  • Calcium Channels, L-Type
  • NFATC Transcription Factors
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin