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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Mitogen-activated protein kinase regulates early phosphorylation and delayed expression of Ca2+/calmodulin-dependent protein kinase II in long-term potentiation.
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Mitogen-activated protein kinase regulates early phosphorylation and delayed expression of Ca2+/calmodulin-dependent protein kinase II in long-term potentiation.

机译:丝裂原活化的蛋白激酶在长期增强中调节早期的磷酸化和Ca2 + /钙调蛋白依赖性蛋白激酶II的延迟表达。

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摘要

Activation of mitogen-activated protein kinase (MAPK) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) are required for numerous forms of neuronal plasticity, including long-term potentiation (LTP). We induced LTP in rat hippocampal area CA1 using theta-pulse stimulation (TPS) paired with beta-adrenergic receptor activation [isoproterenol (ISO)], a protocol that may be particularly relevant to normal patterns of hippocampal activity during learning. This stimulation resulted in a transient phosphorylation of p42 MAPK, and the resulting LTP was MAPK dependent. In addition, CaMKII was regulated in two, temporally distinct ways after TPS-ISO: a transient rise in the fraction of phosphorylated CaMKII and a subsequent persistent increase in CaMKII expression. The increases in MAPK and CaMKII phosphorylation were strongly colocalized in the dendrites and cell bodies of CA1 pyramidal cells, and both the transient phosphorylation and delayed expression of CaMKII were prevented by inhibiting p42/p44 MAPK. These results establish a novel bimodal regulation of CaMKII by MAPK, which may contribute to both post-translational modification and increased gene expression.
机译:多种形式的神经元可塑性,包括长期增强(LTP),都需要激活有丝分裂原激活的蛋白激酶(MAPK)和Ca(2 +)/钙调蛋白依赖性蛋白激酶II(CaMKII)。我们使用theta-pulse刺激(TPS)与β-肾上腺素能受体激活[异丙肾上腺素(ISO)]配对诱导大鼠海马区CA1的LTP,该协议可能与学习过程中海马活动的正常模式特别相关。这种刺激导致p42 MAPK瞬时磷酸化,并且所产生的LTP依赖于MAPK。此外,在TPS-ISO之后,CaMKII以两种在时间上不同的方式进行调节:磷酸化CaMKII的比例短暂升高,随后CaMKII表达持续升高。 MAPK和CaMKII磷酸化的增加强烈共定位于CA1锥体细胞的树突和细胞体中,并且通过抑制p42 / p44 MAPK可以防止CaMKII的瞬时磷酸化和延迟表达。这些结果建立了一种新型的通过MAPK调控CaMKII的双峰调节,这可能有助于翻译后修饰和基因表达的增加。

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