Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan
Chia Yu Chang
Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien City, Taiwan; Department of Medical Research and Neuroscience Center, Buddhist Tzu Chi General Hospital, Hualien City, Taiwan
Horng Jyh Harn
Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien City, Taiwan; Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien City, Taiwan
Shinn Zong Lin
Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien City, Taiwan; Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien City, Taiwan
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.
