AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2+ channel activity and nuclear signaling

Neuron. 2007 Jul 19;55(2):261-75. doi: 10.1016/j.neuron.2007.06.032.


Neuronal L-type calcium channels contribute to dendritic excitability and activity-dependent changes in gene expression that influence synaptic strength. Phosphorylation-mediated enhancement of L-type channels containing the CaV1.2 pore-forming subunit is promoted by A-kinase anchoring proteins (AKAPs) that target cAMP-dependent protein kinase (PKA) to the channel. Although PKA increases L-type channel activity in dendrites and dendritic spines, the mechanism of enhancement in neurons remains poorly understood. Here, we show that CaV1.2 interacts directly with AKAP79/150, which binds both PKA and the Ca2+/calmodulin-activated phosphatase calcineurin (CaN). Cotargeting of PKA and CaN by AKAP79/150 confers bidirectional regulation of L-type current amplitude in transfected HEK293 cells and hippocampal neurons. However, anchored CaN dominantly suppresses PKA enhancement of the channel. Additionally, activation of the transcription factor NFATc4 via local Ca2+ influx through L-type channels requires AKAP79/150, suggesting that this signaling complex promotes neuronal L channel signaling to the nucleus through NFATc4.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • COS Cells
  • Calcineurin / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Humans
  • Leucine Zippers / physiology
  • NFATC Transcription Factors / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Nuclear Envelope / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology


  • A Kinase Anchor Proteins
  • AKAP5 protein, human
  • Adaptor Proteins, Signal Transducing
  • Akap5 protein, rat
  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • NFATC Transcription Factors
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin