Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells

Yu Fukuda; Takao Fukui; Chika Hikichi; Tomomasa Ishikawa; Kenichiro Murate; Takeshi Adachi; Hideki Imai; Koki Fukuhara; Akihiro Ueda; Allen P. Kaplan; Tatsuro Mutoh

doi:10.1016/j.brainres.2014.11.041

Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells

Yu Fukuda, Takao Fukui, Chika Hikichi, Tomomasa Ishikawa, Kenichiro Murate, Takeshi Adachi, Hideki Imai, Koki Fukuhara, Akihiro Ueda, Allen P. Kaplan, Tatsuro Mutoh

Neurology & Neuroscience

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	13-21
Number of pages	9
Journal	Brain Research
Volume	1596
DOIs	https://doi.org/10.1016/j.brainres.2014.11.041
Publication status	Published - 30-01-2015

All Science Journal Classification (ASJC) codes

General Neuroscience
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2014.11.041

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title = "Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells",

abstract = "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{\textregistered}) 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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author = "Yu Fukuda and Takao Fukui and Chika Hikichi and Tomomasa Ishikawa and Kenichiro Murate and Takeshi Adachi and Hideki Imai and Koki Fukuhara and Akihiro Ueda and Kaplan, {Allen P.} and Tatsuro Mutoh",

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doi = "10.1016/j.brainres.2014.11.041",

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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

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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KW - NGF signaling

KW - Neurotropin

KW - Trk tyrosinekinase

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Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells

Abstract

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