Nogo-A-?20/EphA4 interaction antagonizes apoptosis of neural stem cells by integrating p38 and JNK MAPK signaling

Nogo-A protein consists of two main extracellular domains: Nogo-66 (rat amino acid [aa] 1019–1083) and Nogo-A-?20 (extracellular, active 180 region), which serve as strong inhibitors axon regeneration in the adult CNS (Central Nervous System). Although receptors S1PR2 HSPGs have been identified binding proteins, it remains at present elusive whether other directly interacting with exist, decrease cell death. On hand, key roles EphA4 regulation glioblastoma, NSCs (Neural Stem Cells) proliferation or differentiation are well understood, but little is known relationship between apoptosis. Thus, we aim to determine can bind affect survival NSCs. Here, discover that EphA4, belonging a member erythropoietin-producing hepatocellular (Eph) family, could be acting high affinity ligand for Nogo-A-?20. Trans-membrane needed Nogo-A-?20-triggered inhibition apoptosis, mediated by balancing p38 inactivation JNK MAPK pathway activation. Finally, predict atomic level essential residues Lys-205, Ile-190, Pro-194 Gln-390, Asn-425, Pro-426 might play critical Nogo-A-?20/EphA4 via molecular docking.