BDNF Reduces eEF2 Phosphorylation and Enhances Novel Protein Synthesis in the Growth Cones of Dorsal Root Ganglia Neurons

Neurochem Res. 2018 Jun;43(6):1242-1249. doi: 10.1007/s11064-018-2541-8. Epub 2018 May 7.

Abstract

The local translation, which is regulated by extracellular stimuli such as guidance molecules, in growth cones of neurons provides a molecular mechanism for axonal development. In this study, we performed immunocytochemistry together with atomic force microscopy to investigate the localization of ribosomal proteins in the growth cones of rat dorsal root ganglion (DRG) neurons. The immunoreactivity of ribosomal protein P0/1/2 and S6, and novel protein synthesis were observed in the central, sterically bulky region of growth cones. Brain derived neurotrophic factor (BDNF) reduced the eEF2 phosphorylation, indicating its activation, and enhanced protein synthesis within 30 min. The effects of BDNF were completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR). These results indicated that BDNF rapidly activates translation and enhances novel protein synthesis in growth cones of DRG though the mTOR signaling.

Keywords: AFM; BDNF; Growth cone; Immunocytochemistry; Local protein synthesis; Local translation; SUnSET method; eEF2.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cells, Cultured
  • Ganglia, Spinal / metabolism*
  • Growth Cones / metabolism*
  • Neurogenesis / drug effects
  • Neurons / metabolism*
  • Protein Biosynthesis / drug effects
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • TOR Serine-Threonine Kinases
  • Sirolimus