The RSK2-RPS6 axis promotes axonal regeneration in the peripheral and central nervous systems
Résumé
Unlike immature neurons and the ones from the peripheral nervous system (PNS), mature neurons from the central nervous system (CNS) cannot regenerate after injury. In the past 15 years, tremendous progress has been made to identify molecules and pathways necessary for neuroprotection and/or axon regeneration after CNS injury. In most regenerative models, phosphorylated ribosomal protein S6 (p-RPS6) is up-regulated in neurons, which is often associated with an activation of the mTOR (mammalian target of rapamycin) pathway. However, the exact contribution of posttranslational modifications of this ribosomal protein in CNS regeneration remains elusive. In this study, we demonstrate that RPS6 phosphorylation is essential for PNS and CNS regeneration in mice. We show that this phosphorylation is induced during the preconditioning effect in dorsal root ganglion (DRG) neurons and that it is controlled by the p90S6 kinase RSK2. Our results reveal that RSK2 controls the preconditioning effect and that the RSK2-RPS6 axis is key for this process, as well as for PNS regeneration. Finally, we demonstrate that RSK2 promotes CNS regeneration in the dorsal column, spinal cord synaptic plasticity, and target innervation leading to functional recovery. Our data establish the critical role of RPS6 phosphorylation controlled by RSK2 in CNS regeneration and give new insights into the mechanisms related to axon growth and circuit formation after traumatic lesion.
Mots clés
CNS
central nervous system CTB
cholera toxin B dpi
days post-injury DRG
dorsal root ganglion mTOR
mammalian target of rapamycin PC
precontionned PNS
peripheral nervous system p-RPS6
phosphorylated ribosomal protein S6 RGC
retina ganglion cell RPS6
ribosomal protein S6 vGAT
vesicular gamma aminobutyric acid transporter Vglut1
vesicular glutamate transporter 1
central nervous system
CTB
cholera toxin B
dpi
days post-injury
DRG
dorsal root ganglion
mTOR
mammalian target of rapamycin
PC
precontionned
PNS
peripheral nervous system
p-RPS6
phosphorylated ribosomal protein S6
RGC
retina ganglion cell
RPS6
ribosomal protein S6
vGAT
vesicular gamma aminobutyric acid transporter
Vglut1
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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