Yuta Ishizuka
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Pathophysiology and Metabolism,
   Position   Assistant Professor
Article types 原著
Language English
Peer review Peer reviewed
Title 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.
Journal Formal name：The Journal of biological chemistry
Abbreviation：J Biol Chem
ISSN code：1083351X/00219258
Domestic / ForeginForegin
Publisher American Society for Biochemistry and Molecular Biology
Volume, Issue, Page 284(39),pp.26340-8
Author and coauthor Nobuyuki Takei, Mihoko Kawamura, Yuta Ishizuka, Naomasa Kakiya, Naoko Inamura, Hisaaki Namba, Hiroyuki Nawa
Publication date 2009/09
Summary 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.
DOI 10.1074/jbc.M109.023010
PMID 19625250