@article{03ff94b2b1ed4797b3e93f0dbd1c9623,
title = "Locally translated mTOR controls axonal local translation in nerve injury",
abstract = "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 b1 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.",
author = "Marco Terenzio and Sandip Koley and Nitzan Samra and Ida Rishal and Qian Zhao and Sahoo, {Pabitra K.} and Anatoly Urisman and Letizia Marvaldi and Oses-Prieto, {Juan A.} and Craig Forester and Cynthia Gomes and Kalinski, {Ashley L.} and {Di Pizio}, Agostina and Ella Doron-Mandel and Perry, {Rotem Ben-Tov} and Indrek Koppel and Twiss, {Jeffery L.} and Burlingame, {Alma L.} and Mike Fainzilber",
note = "Acknowledgments: We thank D. Gordon, N. Korem, A. Lin, N. Okladnikov, and E. Kanevskaya for excellent assistance; V. Kiss and V. Shinder for professional microscopy support; S. Ben-Dor for help with guide RNA design; R. Haffner-Krausz for mouse genome editing; and R. Rotkopf for statistical consultations. Funding: This work was supported by funding from the European Research Council (Neurogrowth, to M.F.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.F., J.L.T., and A.L.B.), the Minerva Foundation (to M.F.), the Israel Science Foundation (1284/13 to M.F.), the Department of Defense Congressionally Mandated Research Program (W81XWH-2013-1-308 OR120042 to J.L.T. and M.F.), the National Institutes of Health (R01-NS041596 to J.L.T. and GM103481 to A.L.B.), and the Company of Biologists (Journal of Cell Science travel grants to I.K. and N.S.). M.T. was supported by a Koshland senior postdoctoral fellowship. M.F. is the incumbent of the Chaya Professorial Chair in Molecular Neuroscience at the Weizmann Institute of Science. J.L.T. is the incumbent of the SmartState Chair in Childhood Neurotherapeutics at the University of South Carolina. Author contributions: M.F. and M.T. designed the study. M.T., S.K., N.S., I.R., Q.Z., P.K.S., A.U., L.M., J.A.O.-P., C.G., A.L.K., A.D.P., R.B.-T.P., E.D.-M., and I.K. performed experiments and data analyses. Q.Z., C.F., A.U., and J.A.O.-P. carried out MS analyses. P.K.S., C.G., and A.L.K. conducted FISH analyses. I.R. performed electron microscopy. M.F., J.L.T., and A.L.B. supervised research. M.F. and M.T. wrote the initial manuscript draft. All authors revised the manuscript and approved the final version.",
year = "2018",
month = mar,
day = "23",
doi = "https://doi.org/10.1126/science.aan1053",
language = "الإنجليزيّة",
volume = "359",
pages = "1416--1421",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6382",
}