Comparisons of SOCS mRNA and protein levels in Xenopus provide insights into optic nerve regenerative success

Brain Res. 2019 Feb 1;1704:150-160. doi: 10.1016/j.brainres.2018.10.012. Epub 2018 Oct 10.

Abstract

In vertebrates from fishes to mammals, optic nerve injury induces increased expression ofSuppressor of Cytokine Signaling 3(SOCS3) mRNA, a modulator of cytokine signaling that is known to inhibit CNS axon regeneration. Unlike amniotes, however, anamniotes successfully regenerate optic axons, despite this increase. To address this seeming paradox, we examined the SOCS3 response to optic nerve injury in the frog,Xenopus laevis, at both the mRNA and protein levels. Far from being only transiently induced, SOCS3 mRNA expression increased throughout regeneration in retinal ganglion cells, but immunostaining and Western blots indicated that this increase was reflected at the protein level in regenerating optic axons but not in ganglion cell bodies. Polysome profiling provided additional evidence that SOCS3 protein levels were regulated post-translationally by demonstrating that the mRNA was efficiently translated in the injured eye. In tumor cells, another member of theSOCS gene family,SOCS2, is known to mediate SOCS3 degradation by targeting it for proteasomal degradation. Unlike the SOCS2 response in mammalian optic nerve injury, SOCS2 expression increased inXenopusretinal ganglion cells after injury, at both the mRNA and protein levels; it was, however, largely absent from both uninjured and regenerating optic axons. We propose a similar degradation mechanism may be spatially restricted inXenopusto keep SOCS3 protein levels sufficiently in check within ganglion cell bodies, where SOCS3 would otherwise inhibit transcription of genes needed for regeneration, but allow them to rise within the axons, where SOCS3 has pro-regenerative effects.

Keywords: Inflammation; Optic nerve regeneration; Protein degradation; Retinal ganglion cells; Suppressor of cytokine signaling; Xenopus laevis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism
  • Nerve Regeneration / physiology*
  • Optic Nerve / metabolism*
  • Optic Nerve Injuries / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retinal Ganglion Cells / metabolism*
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Xenopus laevis

Substances

  • RNA, Messenger
  • Suppressor of Cytokine Signaling Proteins