The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon regeneration

Nature Communications

Volumn 5, Issue , 2014, Pages

  Yang, Liu ^a   Miao, Linqing ^a   Liang, Feisi ^a   Huang, Haoliang ^a   Teng, Xiuyin ^a   Li, Shaohua ^a,b   Nuriddinov, Jaloliddin ^c   Selzer, Michael E ^a   Hu, Yang ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^c Temple University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INITIATION FACTOR 4E BINDING PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN; S6K1 PROTEIN; UNCLASSIFIED DRUG; CARRIER PROTEIN; EIF4EBP1 PROTEIN, MOUSE; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; PHOSPHOPROTEIN; PTEN PROTEIN, MOUSE; RPS6KA1 PROTEIN, MOUSE; S6 KINASE; TARGET OF RAPAMYCIN KINASE;

BRAIN; GENE EXPRESSION; INHIBITION; INJURY; NEUROLOGY; PROTEIN; REGROWTH; RODENT;

ANIMAL TISSUE; ARTICLE; CENTRAL NERVOUS SYSTEM; GENE DELETION; HUMAN; MALE; MOUSE; NERVE FIBER; NERVE FIBER GROWTH; NERVE FIBER REGENERATION; NONHUMAN; PROTEIN FUNCTION; ANIMAL; ANIMAL MODEL; AXON; C57BL MOUSE; CELL SURVIVAL; CYTOLOGY; DEFICIENCY; GENETICS; KNOCKOUT MOUSE; NERVE REGENERATION; OPTIC NERVE INJURY; PATHOPHYSIOLOGY; PHYSIOLOGY; RETINA GANGLION CELL; SIGNAL TRANSDUCTION;

EUKARYOTA; MAMMALIA;

ANIMALS; AXONS; CARRIER PROTEINS; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MODELS, ANIMAL; MULTIPROTEIN COMPLEXES; NERVE REGENERATION; OPTIC NERVE INJURIES; PHOSPHOPROTEINS; PTEN PHOSPHOHYDROLASE; RETINAL GANGLION CELLS; RIBOSOMAL PROTEIN S6 KINASES, 90-KDA; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84923366621     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms6416     Document Type: Article

References (45)

1. Schwab, M. E. & Bartholdi, D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol. Rev. 76, 319-370 (1996).
2. Goldberg, J. L., Klassen, M. P., Hua, Y. & Barres, B. A. Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 296, 1860-1864 (2002).
3. Fitch, M. T. & Silver, J. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209, 294-301 (2008).
4. Park, K. K., Liu, K., Hu, Y., Kanter, J. L. & He, Z. PTEN/mTOR and axon regeneration. Exp. Neurol. 223, 45-50 (2010).
5. Yiu, G. & He, Z. Glial inhibition of CNS axon regeneration. Nat. Rev. Neurosci. 7, 617-627 (2006).
6. Park, K. K. et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322, 963-966 (2008).
7. Liu, K. et al. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat. Neurosci. 13, 1075-1081 (2010).
8. Abe, N., Borson, S. H., Gambello, M. J., Wang, F. & Cavalli, V. Mammalian target of rapamycin (mTOR) activation increases axonal growth capacity of injured peripheral nerves. J. Biol. Chem. 285, 28034-28043 (2010).
9. Christie, K. J., Webber, C. A., Martinez, J. A., Singh, B. & Zochodne, D. W. PTEN inhibition to facilitate intrinsic regenerative outgrowth of adult peripheral axons. J. Neurosci. 30, 9306-9315 (2010).
10. Song, Y. et al. Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam. Genes Dev. 26, 1612-1625 (2012).
11. Byrne, A. B. et al. Insulin/IGF1 signaling inhibits age-dependent axon regeneration. Neuron 81, 561-573 (2014).
12. Ma, X. M. & Blenis, J. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell. Biol. 10, 307-318 (2009).
13. Laplante, M. & Sabatini, D. M. mTOR signaling in growth control and disease. Cell 149, 274-293 (2012).
14. Song, M. S., Salmena, L. & Pandolfi, P. P. The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell. Biol. 13, 283-296 (2012).
15. Sun, F. et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 480, 372-375 (2011).
16. Kurimoto, T. et al. Long-distance axon regeneration in the mature optic nerve: contributions of oncomodulin, cAMP, and pten gene deletion. J. Neurosci. 30, 15654-15663 (2010).
17. Leibinger, M., Andreadaki, A. & Fischer, D. Role of mTOR in neuroprotection and axon regeneration after inflammatory stimulation. Neurobiol. Dis. 46, 314-324 (2012).
18. Lu, P. et al. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell 150, 1264-1273 (2012).
19. Hay, N. & Sonenberg, N. Upstream and downstream of mTOR. Genes Dev. 18, 1926-1945 (2004).
20. Hannan, K. M. et al. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol. Cell. Biol. 23, 8862-8877 (2003).
21. Duvel, K. et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 39, 171-183 (2010).
22. Magnuson, B., Ekim, B. & Fingar, D. C. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem. J. 441, 1-21 (2012).
23. Ohanna, M. et al. Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat. Cell. Biol. 7, 286-294 (2005).
24. Dowling, R. J. et al. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 328, 1172-1176 (2010).
25. Shima, H. et al. Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J. 17, 6649-6659 (1998).
26. Pende, M. et al. Hypoinsulinaemia, glucose intolerance and diminished betacell size in S6K1-deficient mice. Nature 408, 994-997 (2000).
27. Pende, M. et al. S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5'-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. Mol. Cell. Biol. 24, 3112-3124 (2004).
28. Dowling, R. J., Zakikhani, M., Fantus, I. G., Pollak, M. & Sonenberg, N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 67, 10804-10812 (2007).
29. Pearson, R. B. et al. The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J. 14, 5279-5287 (1995).
30. Pang, J. J. et al. Comparative analysis of in vivo and in vitro AAV vector transduction in the neonatal mouse retina: effects of serotype and site of administration. Vision Res. 48, 377-385 (2008).
31. Hu, Y. et al. Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron 73, 445-452 (2012).
32. Guy, J. et al. Efficiency and safety of AAV-mediated gene delivery of the human ND4 complex I subunit in the mouse visual system. Invest. Ophthalmol. Vis. Sci. 50, 4205-4214 (2009).
33. Le Bacquer, O. et al. Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. J. Clin. Invest. 117, 387-396 (2007).
34. Radimerski, T., Montagne, J., Hemmings-Mieszczak, M. & Thomas, G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 16, 2627-2632 (2002).
35. Um, S. H. et al. Absence of S6K1 protects against age-and diet-induced obesity while enhancing insulin sensitivity. Nature 431, 200-205 (2004).
36. Thoreen, C. C. et al. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109-113 (2012).
37. Zhang, H. H., Lipovsky, A. I., Dibble, C. C., Sahin, M. & Manning, B. D. S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol. Cell 24, 185-197 (2006).
38. Dill, J., Wang, H., Zhou, F. & Li, S. Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS. J. Neurosci. 28, 8914-8928 (2008).
39. Saijilafu et al. PI3K-GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1. Nat. Commun. 4, 2690 (2013).
40. Zhang, B. Y. et al. Akt-independent GSK3 inactivation downstream of PI3K signaling regulates mammalian axon regeneration. Biochem. Biophys. Res. Commun. 443, 743-748 (2014).
41. Narayanan, U. et al. S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade. J. Biol. Chem. 283, 18478-18482 (2008).
42. Harada, H., Andersen, J. S., Mann, M., Terada, N. & Korsmeyer, S. J. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc. Natl Acad. Sci. USA 98, 9666-9670 (2001).
43. Hubert, T., Wu, Z., Chisholm, A. D. & Jin, Y. S6 kinase inhibits intrinsic axon regeneration capacity via AMP kinase in Caenorhabditis elegans. J. Neurosci. 34, 758-763 (2014).
44. Yu, Y. et al. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-1326 (2011).
45. Hsu, P. P. et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-1322 (2011).