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


ABSTRACT: Using mouse optic nerve (ON) crush as a CNS injury model, we and others have found that activation of the mammalian target of rapamycin complex 1 (mTORC1) in mature retinal ganglion cells by deletion of the negative regulators, phosphatase and tensin homologue (PTEN), and tuberous sclerosis 1 promotes ON regeneration. mTORC1 activation inhibits eukaryotic translation initiation factor 4E-binding protein (4E-BP) and activates ribosomal protein S6 kinase 1 (S6K1), both of which stimulate translation. We reasoned that mTORC1's regeneration-promoting effects might be separable from its deleterious effects by differential manipulation of its downstream effectors. Here we show that S6K1 activation, but not 4E-BP inhibition, is sufficient to promote axon regeneration. However, inhibition of 4E-BP is required for PTEN deletion-induced axon regeneration. Both activation and inhibition of S6K1 decrease the effect of PTEN deletion on axon regeneration, implicating a dual role of S6K1 in regulating axon growth.

SUBMITTER: Yang L 

PROVIDER: S-EPMC4228696 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Yang Liu L   Miao Linqing L   Liang Feisi F   Huang Haoliang H   Teng Xiuyin X   Li Shaohua S   Nuriddinov Jaloliddin J   Selzer Michael E ME   Hu Yang Y  

Nature communications 20141110


Using mouse optic nerve (ON) crush as a CNS injury model, we and others have found that activation of the mammalian target of rapamycin complex 1 (mTORC1) in mature retinal ganglion cells by deletion of the negative regulators, phosphatase and tensin homologue (PTEN), and tuberous sclerosis 1 promotes ON regeneration. mTORC1 activation inhibits eukaryotic translation initiation factor 4E-binding protein (4E-BP) and activates ribosomal protein S6 kinase 1 (S6K1), both of which stimulate translati  ...[more]

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