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Locally translated mTOR controls axonal local translation in nerve injury

2018; American Association for the Advancement of Science; Volume: 359; Issue: 6382 Linguagem: Inglês

10.1126/science.aan1053

1095-9203

Marco Terenzio, Sandip Koley, Nitzan Samra, Ida Rishal, Qian Zhao, Pabitra K. Sahoo, Anatoly Urisman, Letizia Marvaldi, Juan A. Osés-Prieto, Craig M. Forester, Cynthia Gomes, Ashley L. Kalinski, Agostina Di Pizio, Ella Doron‐Mandel, Rotem Ben-Tov Perry, Indrek Koppel, Jeffery L. Twiss, Alma L. Burlingame, Mike Fainzilber,

Neuroscience and Neural Engineering

How is protein synthesis initiated locally in neurons? We found that mTOR (mechanistic target of rapamycin) was activated and then up-regulated in injured axons, owing to local translation of mTOR messenger RNA (mRNA). This mRNA was transported into axons by the cell size-regulating RNA-binding protein nucleolin. Furthermore, mTOR controlled local translation in injured axons. This included regulation of its own translation and that of retrograde injury signaling molecules such as importin β1 and STAT3 (signal transducer and activator of transcription 3). Deletion of the mTOR 3' untranslated region (3'UTR) in mice reduced mTOR in axons and decreased local translation after nerve injury. Both pharmacological inhibition of mTOR in axons and deletion of the mTOR 3'UTR decreased proprioceptive neuronal survival after nerve injury. Thus, mRNA localization enables spatiotemporal control of mTOR pathways regulating local translation and long-range intracellular signaling.