Neu3 sialidase-mediated ganglioside conversion is necessary for axon regeneration and is blocked in CNS axons

Sunil Kappagantula, Melissa Renee Andrews, Menghon Cheah, Jose' Abad-Rodriguez, Carlos G Dotti, James W Fawcett

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

PNS axons have a high intrinsic regenerative ability, whereas most CNS axons show little regenerative response. We show that activation of Neu3 sialidase, also known as Neuraminidase-3, causing conversion of GD1a and GT1b to GM1 ganglioside, is an essential step in regeneration occurring in PNS (sensory) but not CNS (retinal) axons in adult rat. In PNS axons, axotomy activates Neu3 sialidase, increasing the ratio of GM1/GD1a and GM1/GT1b gangliosides immediately after injury in vitro and in vivo. No change in the GM1/GD1a
ratio after axotomy was observed in retinal axons (in vitro and in vivo), despite the presence of Neu3 sialidase. Externally applied sialidase converted GD1a ganglioside to GM1 and rescued axon regeneration in CNS axons and in PNS axons after Neu3 sialidase blockade. Neu3 sialidase activation in DRGs is initiated by an influx of extracellular calcium, activating P38MAPK and then Neu3 sialidase. Ganglioside conversion by Neu3 sialidase further activates the ERK pathway. In CNS axons, P38MAPK and Neu3 sialidase were not activated by
axotomy.
Original languageEnglish
Pages (from-to)2477-2492
JournalThe Journal of Neuroscience
Volume34
Issue number7
DOIs
Publication statusPublished - 12 Feb 2014

Keywords

  • Axon regeneration
  • Axotomy
  • Gangliosides
  • Neu3 sialidase

Fingerprint

Dive into the research topics of 'Neu3 sialidase-mediated ganglioside conversion is necessary for axon regeneration and is blocked in CNS axons'. Together they form a unique fingerprint.

Cite this