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Enhancement of translation elongation in neurons by brain‐derived neurotrophic factor: Implications for mammalian target of rapamycin signaling
Author(s) -
Inamura Naoko,
Nawa Hiroyuki,
Takei Nobuyuki
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03466.x
Subject(s) - phosphorylation , elongation factor , eukaryotic translation elongation factor 1 alpha 1 , brain derived neurotrophic factor , microbiology and biotechnology , ribosomal protein s6 , pi3k/akt/mtor pathway , kinase , translation (biology) , ribosomal s6 kinase , biology , protein kinase a , neurotrophic factors , elongation , signal transduction , p70 s6 kinase 1 , protein kinase b , protein phosphorylation , biochemistry , ribosome , materials science , receptor , rna , messenger rna , ultimate tensile strength , metallurgy , gene
The effects and signaling mechanisms of brain‐derived neurotrophic factor (BDNF) on translation elongation were investigated in cortical neurons. BDNF increased the elongation rate approximately twofold, as determined by measuring the ribosomal transit time. BDNF‐accelerated elongation was inhibited by rapamycin, implicating the mammalian target of rapamycin (mTOR). To explore the mechanisms underlying these effects, we examined the protein phosphorylation cascades that lead to the activation of translation elongation in neurons. BDNF increased eukaryote elongation factor 1A (eEF1A) phosphorylation and decreased eEF2 phosphorylation. Whereas eEF2 phosphorylation levels altered by BDNF were inhibited by rapamycin, eEF1A phosphorylation was not affected by rapamycin or PD98059, a mitogen‐activated protein kinase kinase (MEK) inhibitor. BDNF induced phosphorylation of eEF2 kinase (Ser366), as well as decreased its kinase activity. All these events were inhibited by rapamycin. Furthermore, mTOR siRNA, which reduced mTOR levels up to 50%, inhibited the BDNF‐induced enhancement in elongation rate and decrease in eEF2 phosphorylation. These results strongly suggest that BDNF enhances translation elongation through the activation of the mTOR–eEF2 pathway.