Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation

Tay, Joyce; Hodgman, Rebecca; Sarkissian, Madathia; Richter, Joel D.

doi:10.1101/gad.1071403

Cited by 53 publications

(49 citation statements)

References 28 publications

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“…In agreement with previous in vitro studies (Tay et al, 2003), we found that CPEB was rapidly dephosphorylated in hippocampal neurons. This suggests that to prolong CPEB phosphorylation, a sufficiently high calcium influx may be necessary for simultaneous activation of CaMKII and PKA through calciumdependent adenylyl cyclases.…”

Section: Discussionsupporting

confidence: 81%

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Atkins¹,

Nozaki²,

Shigeri³

et al. 2004

J. Neurosci.

137

131

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Phosphorylation of cytoplasmic polyadenylation element binding protein (CPEB) regulates protein synthesis in hippocampal dendrites. CPEB binds the 3Ј 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/calmodulindependent 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 3Ј 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.

show abstract

Section: Discussionsupporting

confidence: 81%

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Atkins¹,

Nozaki²,

Shigeri³

et al. 2004

J. Neurosci.

137

131

View full text Add to dashboard Cite

show abstract

“…(F) Ligation-mediated polyadenylation test (LM-PAT) assay was used to estimate the poly(A) tail length of p53 mRNA in wildtype and shCPEB knockdown cells. similar to that which occurs in vertebrate germ cells (Tay and Richter 2001;Tay et al 2003;Barnard et al 2004;Richter 2006, 2007;Richter 2007). If this is the case, then other factors such as Gld2 and PARN, which mediate CPEB-directed polyadenylation in oocytes, may have the same function in human fibroblasts, and a reduction in their steady state levels might modulate senescence.…”

Section: Discussionmentioning

confidence: 99%

CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation

Burns¹,

Richter²

2008

Genes Dev.

Self Cite

126

111

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“…For Western blotting, protein extracts were prepared according to Cao et al (2005), or, for hippocampal slices, flash-frozen tissue was disrupted by sonication in 1% SDS or directly in sample buffer. CPEB-1 antibody has been described by Tay et al (2003) or purchased from Affinity Bioreagents; c-Jun antibody was a gift from Roger Davis (University of Massachusetts Medical School, Worcester, MA) or was purchased from Cell Signaling Technologies.…”

Section: Methodsmentioning

confidence: 99%

A Molecular Circuit Composed of CPEB-1 and c-Jun Controls Growth Hormone-Mediated Synaptic Plasticity in the Mouse Hippocampus

Zearfoss¹,

Alarcón²,

Trifilieff³

et al. 2008

J. Neurosci.

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Cytoplasmic polyadenylation element binding protein 1 (CPEB-1) resides at postsynaptic sites in hippocampal neurons in which it controls polyadenylation-induced translation. CPEB-1 knock-out (KO) mice display defects in some forms of synaptic plasticity and hippocampal-dependent memories. To identify CPEB-1-regulated mRNAs, we used proteomics to compare polypeptides in wild-type (WT) and CPEB-1 KO hippocampus. Growth hormone (GH) was reduced in the KO hippocampus, as were the GH signaling molecules phospho-JAK2 and phospho-STAT3. GH mRNA and pre-mRNA were reduced in the KO hippocampus, suggesting that CPEB-1 controls GH transcription. The transcription factor c-Jun, which binds the GH promoter, was also reduced in the KO hippocampus, as was its ability to coimmunoprecipitate chromatin containing the GH promoter. CPEB-1 binds c-Jun 3Ј untranslated region CPEs in vitro and coimmunoprecipitates c-Jun RNA in vivo. GH induces long-term potentiation (LTP) when applied to hippocampal slices from WT and CPEB-1 KO mice, but the magnitude of LTP induced by GH in KO mice is reduced. Pretreatment with GH did not reverse the LTP deficit observed in KO mice after theta-burst stimulation (TBS). Cordycepin, an inhibitor of polyadenylation, disrupted LTP induced by either GH application or TBS. Finally, GH application to hippocampal slices induced JAK2 phosphorylation in WT but not KO animals. These results indicate that CPEB-1 control of c-Jun mRNA translation regulates GH gene expression and resulting downstream signaling events (e.g., synaptic plasticity) in the mouse hippocampus.

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Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation

Cited by 53 publications

References 28 publications

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

Cytoplasmic Polyadenylation Element Binding Protein-Dependent Protein Synthesis Is Regulated by Calcium/Calmodulin-Dependent Protein Kinase II

CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation

A Molecular Circuit Composed of CPEB-1 and c-Jun Controls Growth Hormone-Mediated Synaptic Plasticity in the Mouse Hippocampus

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