Title

N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

5-1-2002

Document Type

Article

Medical Subject Headings

Amino Acid Sequence; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Female; Hippocampus; Molecular Sequence Data; Oocytes; Phosphorylation; Polyadenylation; Protein-Serine-Threonine Kinases; RNA, Messenger; RNA-Binding Proteins; Rats; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Synapses; Transcription Factors; Xenopus; *Xenopus Proteins; *mRNA Cleavage and Polyadenylation Factors

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: EMBO J. 2002 May 1;21(9):2139-48. Link to article on publisher's site

Related Resources

Link to article in PubMed