Locally translated mTOR controls axonal local translation in nerve injury.
Locally translated mTOR controls axonal local translation in nerve injury.
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局部翻译的MTOR控制神经损伤中的轴突局部翻译。
DOI：
10.1126/science.aan1053
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发表时间：
2018-03-23
期刊：
影响因子：
--
通讯作者：
Fainzilber M
中科院分区：
文献类型：
--
作者：
Terenzio M;Koley S;Samra N;Rishal I;Zhao Q;Sahoo PK;Urisman A;Marvaldi L;Oses-Prieto JA;Forester C;Gomes C;Kalinski AL;Di Pizio A;Doron-Mandel E;Perry RB;Koppel I;Twiss JL;Burlingame AL;Fainzilber M
蛋白质合成是如何在神经元中局部启动的？我们发现，mTOR被激活，然后上调损伤的轴突，由于mTOR mRNA的本地翻译。这种mRNA被细胞大小调节RNA结合蛋白核仁素转运到轴突中。此外，mTOR控制损伤轴突的局部翻译。这包括调节其自身的翻译和逆行损伤信号分子如importin β1和STAT 3的翻译。小鼠mTOR 3′UTR的缺失减少了轴突中的mTOR，并减少了神经损伤后的局部翻译。轴突中mTOR的药理学抑制和mTOR 3′UTR缺失均降低神经损伤后本体感受神经元的存活率。因此，mRNA定位使得能够时空控制调节局部翻译和长距离细胞内信号传导的mTOR途径。
How is protein synthesis initiated locally in neurons? We found that mTOR was activated and then upregulated in injured axons, owing to local translation of mTOR 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. Deletion of the mTOR 3′UTR in mice reduced mTOR in axons and decreased local translation after nerve injury. Both pharmacological inhibition of mTOR in axons and mTOR 3′UTR deletion decreased proprioceptive neuronal survival after nerve injury. Thus, mRNA localization enables spatiotemporal control of mTOR pathways regulating local translation and long range intracellular signaling.
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DOI：
10.1083/jcb.201212089
发表时间：
2013-07-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sosanya NM;Huang PP;Cacheaux LP;Chen CJ;Nguyen K;Perrone-Bizzozero NI;Raab-Graham KF
通讯作者：
Raab-Graham KF
影响因子：
3
作者：
Rishal, Ida;Michaelevski, Izhak;Rozenbaum, Meir;Shinder, Vera;Medzihradszky, Katalin F.;Burlingame, Alma L.;Fainzilber, Mike
通讯作者：
Fainzilber, Mike
影响因子：
16.2
作者：
Perry RB;Doron-Mandel E;Iavnilovitch E;Rishal I;Dagan SY;Tsoory M;Coppola G;McDonald MK;Gomes C;Geschwind DH;Twiss JL;Yaron A;Fainzilber M
通讯作者：
Fainzilber M
影响因子：
11.4
作者：
Ben-Yaakov, Keren;Dagan, Shachar Y.;Fainzilber, Mike
通讯作者：
Fainzilber, Mike
影响因子：
10.5
作者：
Kobayashi, Mariko;Wilson, Angus C.;Mohr, Ian
通讯作者：
Mohr, Ian