학술논문
Locally translated mTOR controls axonal local translation in nerve injury
Document Type
Author abstract
Author
Terenzio, Marco; Koley, Sandip; Samra, Nitzan; Rishal, Ida; Zhao, Qian; Sahoo, Pabitra K.; Urisman, Anatoly; Marvaldi, Letizia; Oses-Prieto, Juan A.; Forester, Craig; Gomes, Cynthia; Kalinski, Ashley L.; Pizio, Agostina Di; Doron-Mandel, Ella; Perry, Rotem Ben-Tov; Koppel, Indrek; Twiss, Jeffery L.; Burlingame, Alma L.; Fainzilber, Mike
Source
Science. March 23, 2018, Vol. 359 Issue 6382, p1416, 6 p.
Subject
Language
English
ISSN
0036-8075
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-bindlng 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 [beta]1 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. 10.1126/science.aan1053