Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites.
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.
Takei
Nobuyuki
N
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan. nobtak@bri.niigata-u.ac.jp
Inamura
Naoko
N
Kawamura
Mihoko
M
Namba
Hisaaki
H
Hara
Kenta
K
Yonezawa
Kazuyoshi
K
Nawa
Hiroyuki
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D009473:Neuronal Plasticity / Q000502:physiology; D009479:Neuropeptides / Q000032:analysis; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000032:analysis / Q000502:physiology*; D034741:RNA, Small Interfering; D000076205:Ras Homolog Enriched in Brain Protein; D051381:Rats; D012097:Repressor Proteins / Q000032:analysis; D020123:Sirolimus / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins; C087693:Rheb protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins; D020123:Sirolimus