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

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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 languageEnglish
Pages (from-to)13-21
Number of pages9
JournalBrain Research
Volume1596
DOIs
Publication statusPublished - 30-01-2015

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Fukuda, Y., Fukui, T., Hikichi, C., Ishikawa, T., Murate, K., Adachi, T., Imai, H., Fukuhara, K., Ueda, A., Kaplan, A. P., & Mutoh, T. (2015). Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells. Brain Research, 1596, 13-21. https://doi.org/10.1016/j.brainres.2014.11.041