RSK1 promotes mammalian axon regeneration by inducing the synthesis of regeneration-related proteins

  • PLoS Biol. 2022 Jun 1;20(6):e3001653. doi: 10.1371/journal.pbio.3001653.
Susu Mao  1 ,  Yuanyuan Chen  1 ,  Wei Feng  1 ,  Songlin Zhou  1 ,  Chunyi Jiang  1 ,  Junjie Zhang  1 ,  Xiaohong Liu  1 ,  Tianmei Qian  1 ,  Kai Liu  2 ,  Yaxian Wang  1 ,  Chun Yao  1 ,  Xiaosong Gu  1  3 ,  Bin Yu  1  3
Affiliations
  • 1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • 2. Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
  • 3. Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Affiliated Hospital of Nantong University, Nantong University, Nantong, China.
PMID: 35648763 DOI: 10.1371/journal.pbio.3001653
Abstract

In contrast to the adult mammalian central nervous system (CNS), the neurons in the peripheral nervous system (PNS) can regenerate their axons. However, the underlying mechanism dictating the regeneration program after PNS injuries remains poorly understood. Combining chemical inhibitor screening with gain- and loss-of-function analyses, we identified p90 ribosomal S6 kinase 1 (RSK1) as a crucial regulator of axon regeneration in dorsal root ganglion (DRG) neurons after sciatic nerve injury (SNI). Mechanistically, RSK1 was found to preferentially regulate the synthesis of regeneration-related proteins using ribosomal profiling. Interestingly, RSK1 expression was up-regulated in injured DRG neurons, but not retinal ganglion cells (RGCs). Additionally, RSK1 overexpression enhanced Phosphatase and tensin homolog (PTEN) deletion-induced axon regeneration in RGCs in the adult CNS. Our findings reveal a critical mechanism in inducing protein synthesis that promotes axon regeneration and further suggest RSK1 as a possible therapeutic target for neuronal injury repair.

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