کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4322597 | 1291719 | 2007 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: AKAP79/150 Anchoring of Calcineurin Controls Neuronal L-Type Ca2+ Channel Activity and Nuclear Signaling AKAP79/150 Anchoring of Calcineurin Controls Neuronal L-Type Ca2+ Channel Activity and Nuclear Signaling](/preview/png/4322597.png)
SummaryNeuronal 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.
Journal: - Volume 55, Issue 2, 19 July 2007, Pages 261–275