RT Journal Article
SR Electronic
T1 Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66-independent targeting of NogoA
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 550921
DO 10.1101/550921
A1 Cheng Yung Lin
A1 Chia Lun Wu
A1 Kok Zhi Lee
A1 You Jei Chen
A1 Po Hsiang Zhang
A1 Chia Yu Chang
A1 Horng Jyh Han
A1 Shinn Zong Lin
A1 Huai Jen Tsai
YR 2019
UL http://biorxiv.org/content/early/2019/02/15/550921.abstract
AB 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 synapse growth and maintenance.