Akap79/150 Anchoring of Calcineurin Controls Neuronal L-type Ca2+ Channel Activity and Nuclear Signaling.
From: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Neuron
- Publish Date: Jul 2007
- ISSN: 0896-6273
- Volume: 55
- Issue: 2
- Pages: 261-75
- Medium: Print
- Language: English
- Citation (JAMA): Oliveria Seth F, Dell'Acqua Mark L, Sather William A, et al. Akap79/150 Anchoring of Calcineurin Controls Neuronal L-type Ca2+ Channel Activity and Nuclear Signaling.. Neuron Jul 2007;55:261-75
Abstract
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.
Mesh Headings (Keywords): A Kinase Anchor Proteins, Adaptor Proteins, Signal Transducing, Animals, COS Cells, Calcineurin, Calcium Channels, L-Type, Cell Line, Cercopithecus aethiops, Cyclic AMP-Dependent Protein Kinases, Hippocampus, Humans, Leucine Zippers, NFATC Transcription Factors, Neurons, Nuclear Envelope, Rats, Rats, Sprague-Dawley, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 17640527
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