CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses.
Long-term changes in synaptic efficacy may require the regulated translation of dendritic mRNAs. While the basis of such regulation is unknown, it seemed possible that some features of translational control in development could be recapitulated in neurons. Polyadenylation-induced translation of oocyte mRNAs requires the cis-acting CPE sequence and the CPE-binding protein CPEB. CPEB is also present in the dendritic layers of the hippocampus, at synapses in cultured neurons, and in postsynaptic densities of adult brain. alpha-CaMKII mRNA, which is localized in dendrites and is necessary for synaptic plasticity and LTP, contains two CPEs. These CPEs are bound by CPEB and mediate polyadenylation-induced translation in injected Xenopus oocytes. In the intact brain, visual experience induces alpha-CaMKII mRNA polyadenylation and translation, suggesting that this process likely occurs at synapses.
Wu
L
L
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655, USA.
Wells
D
D
Tay
J
J
Mendis
D
D
Abbott
M A
MA
Barnitt
A
A
Quinlan
E
E
Heynen
A
A
Fallon
J R
JR
Richter
J D
JD
D000818:Animals; D001921:Brain / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000166:cytology; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D014981:Xenopus; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors
C490388:Cpeb1 protein, Xenopus; C490387:Cpeb1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases