Ecto-domain phosphorylation promotes functional recovery from spinal cord injury.
Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP.
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Kenji
K
Suehiro
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yuka
Y
Nakamura
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Shuai
S
Xu
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Youichi
Y
Uda
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Takafumi
T
Matsumura
Department of Systems Biology, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Yoshiaki
Y
Yamaguchi
DDepartment of Systems Biology, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Hitoshi
H
Okamura
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.
Toshihide
T
Yamashita
Department of Nanobio Drug Discovery Science, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
Yoshinori
Y
Takei
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009185:Myelin Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology; D000070816:Nogo Receptor 1; D010766:Phosphorylation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C486581:Rtn4r protein, rat; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases