RT Journal Article
SR Electronic
T1 Neu3 Sialidase-Mediated Ganglioside Conversion Is Necessary for Axon Regeneration and Is Blocked in CNS Axons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2477
OP 2492
DO 10.1523/JNEUROSCI.4432-13.2014
VO 34
IS 7
A1 Sunil Kappagantula
A1 Melissa R. Andrews
A1 Menghon Cheah
A1 José Abad-Rodriguez
A1 Carlos G. Dotti
A1 James W. Fawcett
YR 2014
UL http://www.jneurosci.org/content/34/7/2477.abstract
AB 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.