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学科主题: 基础医学
题名:
AKAP79/150 Impacts Intrinsic Excitability of Hippocampal Neurons through Phospho-Regulation of A-type K+ Channel Trafficking
作者: Lin, Lin1; Sun, Wei1,2,3; Kung, Faith1; Dell&prime1; Acqua, Mark L.4; Hoffman, Dax A.1
刊名: JOURNAL OF NEUROSCIENCE
发表日期: 2011-01-26
DOI: 10.1523/JNEUROSCI.5383-10.2011
卷: 31, 期:4, 页:1323-1332
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: LONG-TERM POTENTIATION ; CA1 PYRAMIDAL NEURONS ; DEPENDENT PROTEIN-KINASE ; NMDA RECEPTOR ACTIVATION ; ANCHORING PROTEIN ; AMPA RECEPTORS ; SYNAPTIC PLASTICITY ; POTASSIUM CHANNELS ; DENDRITIC EXCITABILITY ; SCAFFOLD PROTEIN
英文摘要:

Kv4.2, as the primary alpha-subunit of rapidly inactivating, A-type voltage-gated K+ (Kv) channels expressed in hippocampal CA1 pyramidal dendrites, plays a critical role in regulating their excitability. Activity-dependent trafficking of Kv4.2 relies on C-terminal protein kinase A (PKA) phosphorylation. A-kinase-anchoring proteins (AKAPs) target PKA to glutamate receptor and ion channel complexes to allow for discrete, local signaling. As part of a previous study, we showed that AKAP79/150 interacts with Kv4.2 complexes and that the two proteins colocalize in hippocampal neurons. However, the nature and functional consequence of their interaction has not been previously explored. Here, we report that the C-terminal domain of Kv4.2 interacts with an internal region of AKAP79/150 that overlaps with its MAGUK (membrane-associated guanylate kinase)-binding domain. We show that AKAP79/150-anchored PKA activity controls Kv4.2 surface expression in heterologous cells and hippocampal neurons. Consistent with these findings, disrupting PKA anchoring led to a decrease in neuronal excitability, while preventing dephosphorylation by the phosphatase calcineurin resulted in increased excitability. These results demonstrate that AKAP79/150 provides a platform for dynamic PKA regulation of Kv4.2 expression, fundamentally impacting CA1 excitability.

语种: 英语
项目资助者: Eunice Kennedy Shriver National Institute of Child Health and Human Development
WOS记录号: WOS:000286655600018
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51984
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA
2.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Beijing 100191, Peoples R China
4.Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA

Recommended Citation:
Lin, Lin,Sun, Wei,Kung, Faith,et al. AKAP79/150 Impacts Intrinsic Excitability of Hippocampal Neurons through Phospho-Regulation of A-type K+ Channel Trafficking[J]. JOURNAL OF NEUROSCIENCE,2011,31(4):1323-1332.
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