NDLI: Brain-derived neurotrophic factor enhances the basal rate of protein synthesis by increasing active eukaryotic elongation factor 2 levels and promoting translation elongation in cortical neurons.

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Brain-derived neurotrophic factor enhances the basal rate of protein synthesis by increasing active eukaryotic elongation factor 2 levels and promoting translation elongation in cortical neurons.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kawamura, Mihoko Takei, Nobuyuki Inamura, Naoko Namba, Hisaaki Nawa, Hiroyuki Kakiya, Naomasa Ishizuka, Yuta
Description	Author Affiliation: Takei N ( Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan. nobtak@bri.niigata-u.ac.jp)
Abstract	The constitutive and activity-dependent components of protein synthesis are both critical for neural function. Although the mechanisms controlling extracellularly induced protein synthesis are becoming clear, less is understood about the molecular networks that regulate the basal translation rate. Here we describe the effects of chronic treatment with various neurotrophic factors and cytokines on the basal rate of protein synthesis in primary cortical neurons. Among the examined factors, brain-derived neurotrophic factor (BDNF) showed the strongest effect. The rate of protein synthesis increased in the cortical tissues of BDNF transgenic mice, whereas it decreased in BDNF knock-out mice. BDNF specifically increased the level of the active, unphosphorylated form of eukaryotic elongation factor 2 (eEF2). The levels of active eEF2 increased and decreased in BDNF transgenic and BDNF knock-out mice, respectively. BDNF decreased kinase activity and increased phosphatase activity against eEF2 in vitro. Additionally, BDNF shortened the ribosomal transit time, an index of translation elongation. In agreement with these results, overexpression of eEF2 enhanced protein synthesis. Taken together, our results demonstrate that the increased level of active eEF2 induced by chronic BDNF stimulation enhances translational elongation processes and increases the total rate of protein synthesis in neurons.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	39
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-09-25
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain-Derived Neurotrophic Factor Pharmacology Neurons Drug Effects Peptide Elongation Factor 2 Metabolism Protein Biosynthesis Animals Blotting, Western Genetics Cells, Cultured Cerebral Cortex Cytology Embryology Cytokines Elongation Factor 2 Kinase Intercellular Signaling Peptides And Proteins Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Knockout Mice, Transgenic Mutation Phosphorylation Reverse Transcriptase Polymerase Chain Reaction Ribosomes Time Factors Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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