PMID- 17064361 OWN - NLM STAT- MEDLINE DCOM- 20070123 LR - 20091119 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 99 IP - 5 DP - 2006 Dec TI - Dual regulation of translation initiation and peptide chain elongation during BDNF-induced LTP in vivo: evidence for compartment-specific translation control. PG - 1328-37 AB - Protein synthesis underlying activity-dependent synaptic plasticity is controlled at the level of mRNA translation. We examined the dynamics and spatial regulation of two key translation factors, eukaryotic initiation factor 4E (eIF4E) and elongation factor-2 (eEF2), during long-term potentiation (LTP) induced by local infusion of brain-derived neurotrophic factor (BDNF) into the dentate gyrus of anesthetized rats. BDNF-induced LTP led to rapid, transient phosphorylation of eIF4E and eEF2, and enhanced expression of eIF4E protein in dentate gyrus homogenates. Infusion of the extracellular signal-regulated kinase (ERK) inhibitor U0126 blocked BDNF-LTP and modulation of the translation factor activity and expression. Quantitative immunohistochemical analysis revealed enhanced staining of phospho-eIF4E and total eIF4E in dentate granule cells. The in vitro synaptodendrosome preparation was used to isolate the synaptic effects of BDNF in the dentate gyrus. BDNF treatment of synaptodendrosomes elicited rapid, transient phosphorylation of eIF4E paralleled by enhanced expression of alpha-calcium/calmodulin-dependent protein kinase II. In contrast, BDNF had no effect on eEF2 phosphorylation state in synaptodendrosomes. The results demonstrate rapid ERK-dependent regulation of the initiation and elongation steps of protein synthesis during BDNF-LTP in vivo. Furthermore, the results suggest a compartment-specific regulation in which initiation is selectively enhanced by BDNF at synapses, while both initiation and elongation are modulated at non-synaptic sites. FAU - Kanhema, Tambudzai AU - Kanhema T AD - Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Bergen, Norway. FAU - Dagestad, Grethe AU - Dagestad G FAU - Panja, Debabrata AU - Panja D FAU - Tiron, Adrian AU - Tiron A FAU - Messaoudi, Elhoucine AU - Messaoudi E FAU - Havik, Bjarte AU - Havik B FAU - Ying, Shui-Wang AU - Ying SW FAU - Nairn, Angus C AU - Nairn AC FAU - Sonenberg, Nahum AU - Sonenberg N FAU - Bramham, Clive R AU - Bramham CR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061025 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Eukaryotic Initiation Factor-4E) RN - 0 (Eukaryotic Initiation Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Peptide Elongation Factor 2) RN - 0 (Peptides) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/metabolism MH - Cell Compartmentation/physiology MH - Dendrites/drug effects/metabolism MH - Dentate Gyrus/drug effects/*metabolism MH - Drug Administration Routes MH - Enzyme Inhibitors/pharmacology MH - Eukaryotic Initiation Factor-4E/genetics/metabolism MH - Eukaryotic Initiation Factors/genetics/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism MH - Immunohistochemistry MH - Long-Term Potentiation/drug effects/*genetics MH - Male MH - Nerve Tissue Proteins/*biosynthesis/genetics MH - Peptide Elongation Factor 2/genetics/metabolism MH - Peptides/metabolism MH - Phosphorylation MH - Presynaptic Terminals/drug effects/metabolism MH - Protein Biosynthesis/*genetics MH - Rats MH - Rats, Sprague-Dawley MH - Synaptic Transmission/drug effects/physiology MH - Synaptosomes/drug effects/metabolism EDAT- 2006/10/27 09:00 MHDA- 2007/01/24 09:00 CRDT- 2006/10/27 09:00 PHST- 2006/10/27 09:00 [pubmed] PHST- 2007/01/24 09:00 [medline] PHST- 2006/10/27 09:00 [entrez] AID - JNC4158 [pii] AID - 10.1111/j.1471-4159.2006.04158.x [doi] PST - ppublish SO - J Neurochem. 2006 Dec;99(5):1328-37. doi: 10.1111/j.1471-4159.2006.04158.x. Epub 2006 Oct 25.