N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses.
Activity-dependent local translation of dendritic mRNAs is one process that underlies synaptic plasticity. Here, we demonstrate that several of the factors known to control polyadenylation-induced translation in early vertebrate development [cytoplasmic polyadenylation element-binding protein (CPEB), maskin, poly(A) polymerase, cleavage and polyadenylation specificity factor (CPSF) and Aurora] also reside at synaptic sites of rat hippocampal neurons. The induction of polyadenylation at synapses is mediated by the N-methyl-D-aspartate (NMDA) receptor, which transduces a signal that results in the activation of Aurora kinase. This kinase in turn phosphorylates CPEB, an essential RNA-binding protein, on a critical residue that is necessary for polyadenylation-induced translation. These data demonstrate a remarkable conservation of the regulatory machinery that controls signal-induced mRNA translation, and elucidates an axis connecting the NMDA receptor to localized protein synthesis at synapses.
Huang
Yi-Shuian
YS
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jung
Mi-Young
MY
Sarkissian
Madathia
M
Richter
Joel D
JD
D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D005260:Female; D006624:Hippocampus / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D010766:Phosphorylation; D026723:Polyadenylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014981:Xenopus / Q000502:physiology; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors
C490388:Cpeb1 protein, Xenopus; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D029867:Xenopus Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases