The Journal of Neuroscience, November 3, 2004, 24(44):9760-9769; doi:10.1523/JNEUROSCI.1427-04.2004
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Cellular/Molecular
Brain-Derived Neurotrophic Factor Induces Mammalian Target of Rapamycin-Dependent Local Activation of Translation Machinery and Protein Synthesis in Neuronal Dendrites
Nobuyuki Takei,1
Naoko Inamura,1
Mihoko Kawamura,1
Hisaaki Namba,1
Kenta Hara,2,3
Kazuyoshi Yonezawa,2,3 and
Hiroyuki Nawa1
1Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan, 2Biosignal Research Center, Kobe University, Kobe 657-8501, Japan, and 3Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
In neurons, perisynaptic or dendritic translation is implicated in synapse-wide alterations of function and morphology triggered by neural activity. The molecular mechanisms controlling local translation activation, however, have yet to be elucidated. Here, we show that local protein synthesis and translational activation in neuronal dendrites are upregulated by brain-derived neurotrophic factor (BDNF) in a rapamycin and small interfering RNA specific for mammalian target of rapamycin (mTOR)-sensitive manner. In parallel, BDNF induced the phosphorylation of tuberin and the activation of mTOR in dendrites and the synaptoneurosome fraction. mTOR activation stimulated translation initiation processes involving both eIF4E/4E-binding protein (4EBP) and p70S6 kinase/ribosomal S6 protein. BDNF induced phosphorylation of 4EBP in isolated dendrites. Moreover, local puff application of BDNF to dendrites triggered S6 phosphorylation in a restricted area. Taken together, these data indicate that mTOR-dependent translation activation is essential for the upregulation of local protein synthesis in neuronal dendrites.
Key words: BDNF; local protein synthesis; mTOR; neuron; raptor; translation; tuberin
Received Oct 2, 2003;
revised September 14, 2004;
accepted September 14, 2004.
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