PUBLICATION
Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA
- Authors
- 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.
- ID
- ZDB-PUB-190801-17
- 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
Citation
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. (2019) Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA. eLIFE. 8:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping