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.
Highlights
(5–7), enhances protein synthesis and activates the translational machinery in central nervous system neurons [8]
We demonstrate that chronic treatment of primary cortical neurons with brain-derived neurotrophic factor (BDNF) increases the level of active, unphosphorylated eukaryotic elongation factor 2 and enhances the rates of elongation and protein synthesis
Immunocytochemistry with anti-microtubule-associated protein 2 antibody revealed that BDNF did not affect cell viability under these culture conditions, protein synthesis rates were calculated from the same cell number
Summary
(5–7), enhances protein synthesis and activates the translational machinery in central nervous system neurons [8]. We demonstrate that chronic treatment of primary cortical neurons with BDNF increases the level of active, unphosphorylated eukaryotic elongation factor 2 (eEF2) and enhances the rates of elongation and protein synthesis. Whereas BDNF increased the total amount of eEF2 protein, it markedly reduced the level of phospho-eEF2, which does not contribute to translation elongation (Fig. 4, D–F).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
