Cytoplasmic polyadenylation element binding protein-dependent protein synthesis is regulated by calcium/calmodulin-cependent protein kinase II

被引:125
作者
Atkins, CM
Nozaki, N
Shigeri, Y
Soderling, TR
机构
[1] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA
[2] Kanagawa Dent Coll, Kanagawa 2388580, Japan
[3] Natl Inst Adv Ind Sci & Technol, Osaka 5638577, Japan
关键词
CPEB; CaMKII; translation; synaptic plasticity; protein phosphatase; protein synthesis; polyadenylation;
D O I
10.1523/JNEUROSCI.0854-04.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Phosphorylation of cytoplasmic polyadenylation element binding protein (CPEB) regulates protein synthesis in hippocampal dendrites. CPEB binds the 3' untranslated region (UTR) of cytoplasmic mRNAs and, when phosphorylated, initiates mRNA polyadenylation and translation. We report that, of the protein kinases activated in the hippocampus during synaptic plasticity, calcium/calmodulin-dependent protein kinase II ( CaMKII) robustly phosphorylated the regulatory site ( threonine 171) in CPEB in vitro. In postsynaptic density fractions or hippocampal neurons, CPEB phosphorylation increased when CaMKII was activated. These increases in CPEB phosphorylation were attenuated by a specific peptide inhibitor of CaMKII and by the general CaM-kinase inhibitor KN-93. Inhibitors of protein phosphatase 1 increased basal CPEB phosphorylation in neurons; this was also attenuated by a CaM-kinase inhibitor. To determine whether CaM-kinase activity regulates CPEB-dependent mRNA translation, hippocampal neurons were transfected with luciferase fused to a 3' UTR containing CPE-binding elements. Depolarization of neurons stimulated synthesis of luciferase; this was abrogated by inhibitors of protein synthesis, mRNA polyadenylation, and CaMKII. These results demonstrate that CPEB phosphorylation and translation are regulated by CaMKII activity and provide a possible mechanism for how dendritic protein synthesis in the hippocampus may be stimulated during synaptic plasticity.
引用
收藏
页码:5193 / 5201
页数:9
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