Dendritic transport and localization of protein kinase Mzeta mRNA: implications for molecular memory consolidation

Protein kinase Mzeta (PKMzeta) is an atypical protein kinase C isoform that has been implicated in the protein synthesis-dependent maintenance of long term potentiation and memory storage in the brain. Synapse-associated kinases are uniquely positioned to promote enduring consolidation of structural...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-12, Vol.279 (50), p.52613-52622
Main Authors: Muslimov, Ilham Aliagaevich, Nimmrich, Volker, Hernandez, Alejandro Ivan, Tcherepanov, Andrew, Sacktor, Todd Charlton, Tiedge, Henri
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological Transport, Active
Cells, Cultured
Dendrites - metabolism
Hippocampus - metabolism
Memory - physiology
Nucleic Acid Conformation
Phosphopyruvate Hydratase - genetics
Phosphopyruvate Hydratase - metabolism
Protein Biosynthesis
Protein Kinase C - genetics
Rats
RNA, Messenger - chemistry
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Small Cytoplasmic - genetics
RNA, Small Cytoplasmic - metabolism
Signal Transduction
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Summary:Protein kinase Mzeta (PKMzeta) is an atypical protein kinase C isoform that has been implicated in the protein synthesis-dependent maintenance of long term potentiation and memory storage in the brain. Synapse-associated kinases are uniquely positioned to promote enduring consolidation of structural and functional modifications at the synapse, provided that kinase mRNA is available on site for local input-specific translation. We now report that the mRNA encoding PKMzeta is rapidly transported and specifically localized to synaptodendritic neuronal domains. Transport of PKMzeta mRNA is specified by two cis-acting dendritic targeting elements (Mzeta DTEs). Mzeta DTE1, located at the interface of the 5'-untranslated region and the open reading frame, directs somato-dendritic export of the mRNA. Mzeta DTE2, in contrast, is located in the 3'-untranslated region and is required for delivery of the mRNA to distal dendritic segments. Colocalization with translational repressor BC1 RNA in hippocampal dendrites suggests that PKMzeta mRNA may be subject to translational control in local domains. Dendritic localization of PKMzeta mRNA provides a molecular basis for the functional integration of synaptic signal transduction and translational control pathways.
ISSN:0021-9258