ZFIN ID: ZDB-PUB-190801-17
Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA
Lin, C.Y., Wu, C.L., Lee, K.Z., Chen, Y.J., Zhang, P.H., Chang, C.Y., Han, H.J., Lin, S.Z., Tsai, H.J.
Date: 2019
Source: eLIFE   8: (Journal)
Registered Authors: Lin, Cheng-Yung, Tsai, Huai-Jen
Keywords: NogoA, Pgk1, developmental biology, human, motoneuron, mouse, muscle, neuroscience, zebrafish
MeSH Terms:
  • Animals
  • Cell Line
  • Humans
  • Mice
  • Mice, Knockout
  • Motor Neurons/physiology*
  • Neuronal Outgrowth*
  • Nogo Proteins/metabolism*
  • Nogo Receptors/metabolism*
  • Phosphoglycerate Kinase/metabolism*
  • Zebrafish
PubMed: 31361595 Full text @ Elife
NogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction with its receptors, Nogo66/NgR. Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways. We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM. Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway. Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1 G93A. Thus, Pgk1 secreted from muscle is detrimental to motoneuron neurite outgrowth and maintenance.