期刊
NEURON
卷 55, 期 2, 页码 261-275出版社
CELL PRESS
DOI: 10.1016/j.neuron.2007.06.032
关键词
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资金
- NHLBI NIH HHS [R01 HL088548-01, R01 HL088548] Funding Source: Medline
- NIMH NIH HHS [R01 MH080291] Funding Source: Medline
- NINDS NIH HHS [NS051963, R01 NS040701, R01 NS035245, NS35245, R56 NS040701, R01 NS035245-08, NS40701, F30 NS051963] Funding Source: Medline
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 Ca(v)1.2 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 Ca(v)1.2 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.
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