PMID- 15525761 OWN - NLM STAT- MEDLINE DCOM- 20050609 LR - 20220309 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 24 IP - 44 DP - 2004 Nov 3 TI - Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. PG - 9760-9 AB - 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. FAU - Takei, Nobuyuki AU - Takei N AD - Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan. nobtak@bri.niigata-u.ac.jp FAU - Inamura, Naoko AU - Inamura N FAU - Kawamura, Mihoko AU - Kawamura M FAU - Namba, Hisaaki AU - Namba H FAU - Hara, Kenta AU - Hara K FAU - Yonezawa, Kazuyoshi AU - Yonezawa K FAU - Nawa, Hiroyuki AU - Nawa H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptides) RN - 0 (RNA, Small Interfering) RN - 0 (Ras Homolog Enriched in Brain Protein) RN - 0 (Repressor Proteins) RN - 0 (Rheb protein, rat) RN - 0 (Tuberous Sclerosis Complex 2 Protein) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.6.5.2 (Monomeric GTP-Binding Proteins) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*physiology MH - Cells, Cultured MH - Cerebral Cortex/cytology/metabolism MH - Dendrites/drug effects/*metabolism MH - Gene Expression Regulation MH - Monomeric GTP-Binding Proteins/analysis MH - Nerve Tissue Proteins/analysis/*biosynthesis MH - Neuronal Plasticity/physiology MH - Neuropeptides/analysis MH - Protein Biosynthesis/drug effects/physiology MH - Protein Kinases/analysis/*physiology MH - RNA, Small Interfering MH - Ras Homolog Enriched in Brain Protein MH - Rats MH - Repressor Proteins/analysis MH - Sirolimus/pharmacology MH - Synaptosomes/metabolism MH - TOR Serine-Threonine Kinases MH - Tuberous Sclerosis Complex 2 Protein MH - Tumor Suppressor Proteins/analysis PMC - PMC6730227 EDAT- 2004/11/05 09:00 MHDA- 2005/06/10 09:00 PMCR- 2005/05/03 CRDT- 2004/11/05 09:00 PHST- 2004/11/05 09:00 [pubmed] PHST- 2005/06/10 09:00 [medline] PHST- 2004/11/05 09:00 [entrez] PHST- 2005/05/03 00:00 [pmc-release] AID - 24/44/9760 [pii] AID - 10.1523/JNEUROSCI.1427-04.2004 [doi] PST - ppublish SO - J Neurosci. 2004 Nov 3;24(44):9760-9. doi: 10.1523/JNEUROSCI.1427-04.2004.