TY - JOUR
T1 - Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells
AU - Fukuda, Yu
AU - Fukui, Takao
AU - Hikichi, Chika
AU - Ishikawa, Tomomasa
AU - Murate, Kenichiro
AU - Adachi, Takeshi
AU - Imai, Hideki
AU - Fukuhara, Koki
AU - Ueda, Akihiro
AU - Kaplan, Allen P.
AU - Mutoh, Tatsuro
N1 - Funding Information:
We are grateful to Dr. Irwin J. Kopin (National Institutes of Health, USA) for helpful discussions. We also thank Ms. Chieko Nishikawa for her excellent technical assistance. This work was supported by the MUSC Foundation for Research Development (Charleston, SC, USA) to A.P.K., and by MEXT-Supported Program for the Strategic Research Foundation at Private Universities 2010–2014 and a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to T.M.
PY - 2015/1/30
Y1 - 2015/1/30
N2 - Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin®) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2 ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.
AB - Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin®) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2 ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.
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U2 - 10.1016/j.brainres.2014.11.041
DO - 10.1016/j.brainres.2014.11.041
M3 - Article
C2 - 25454796
AN - SCOPUS:84919768205
VL - 1596
SP - 13
EP - 21
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
ER -