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 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.
Muslimov
Ilham Aliagaevich
IA
Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
Nimmrich
Volker
V
Hernandez
Alejandro Ivan
AI
Tcherepanov
Andrew
A
Sacktor
Todd Charlton
TC
Tiedge
Henri
H
D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D009690:Nucleic Acid Conformation; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020733:RNA, Small Cytoplasmic / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D000099221:Protein Kinase C zeta
D010751:Phosphopyruvate Hydratase; D011493:Protein Kinase C; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D000099221:Protein Kinase C zeta; C117734:BC1 RNA