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

Susu Mao; Yuanyuan Chen; Wei Feng; Songlin Zhou; Chunyi Jiang; Junjie Zhang; Xiaohong Liu; Tianmei Qian; Kai Liu; Yaxian Wang; Chun Yao; Xiaosong Gu; Bin Yu

doi:10.1371/journal.pbio.3001653

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. eCollection 2022 Jun.

Authors

Susu Mao¹, Yuanyuan Chen¹, Wei Feng¹, Songlin Zhou¹, Chunyi Jiang¹, Junjie Zhang¹, Xiaohong Liu¹, Tianmei Qian¹, Kai Liu², Yaxian Wang¹, Chun Yao¹, 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons* / metabolism
Ganglia, Spinal / metabolism
Mammals
Nerve Regeneration* / physiology
Protein Serine-Threonine Kinases
Retinal Ganglion Cells / metabolism

Substances

Protein Serine-Threonine Kinases

Grants and funding

This work was supported by the National Key R&D Program of China (http://www.most.gov.cn; 2017YFA0104701 to BY, 2021YFA1201402 to SM, 2021YFA1201404 to BY); the National Natural Science Foundation of China (http://www.nsfc.gov.cn/; 32130060 to XG, 32071034 to BY, 31700925 to SM); the Natural Science Foundation of Jiangsu Province (http://kxjst.jiangsu.gov.cn/; BK20202013 to XG); Collegiate Natural Science Fund of Jiangsu Province (http://jyt.jiangsu.gov.cn/; 21KJA180002 to SM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.