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Neurotrophin binding to the p75 neurotrophin receptor is necessary but not sufficient to mediate NGF-effects on APP secretion in PC-12 cells

  • S. Roßner
  • U. Ueberham
  • R. Schliebs
  • J. R. Perez-Polo
  • V. Bigl
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 54)

Summary

In the present study the pheochromocytoma cell line (PC-12) was used as a model system to determine the role of the two neurotrophin receptors in the regulation of amyloid precursor protein (APP) secretion by nerve growth factor (NGF). To stimulate TrkA and/or p75NTR signaling in PC-12 cells, we used NGF, brain-derived neurotrophic factor (BDNF), and NGF in the presence of an excess of BDNF or the monoclonal antibody 192IgG, to block p75NTR binding to NGF. Our results demonstrate that NGF stimulates APP secretion in a dose dependent fashion with maximum effects at 10ng/ml, known to saturate high-affinity NGF binding sites. Treatment of PC-12 cells with varying concentrations of BDNF, l–l,000ng/ml, did not alter APP secretion, suggesting that binding to p75NTR alone is not sufficient to affect APP secretion. When blocking NGF binding to p75NTR with BDNF or 192IgG, on the other hand, NGF effects on APP secretion were abolished. These findings suggest that in cells expressing p75NTR and TrkA receptors, binding of NGF to the p75NTR is required to mediate NGF effects on APP secretion. Our data are also consistent with a proposed function of the p75NTR in receptor recruitment and “presentation” of NGF to receptors.

Keywords

Nerve Growth Factor Amyloid Precursor Protein Neurotrophin Receptor TrkA Receptor Nerve Growth Factor Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag/Wien 1998

Authors and Affiliations

  • S. Roßner
    • 1
  • U. Ueberham
    • 1
  • R. Schliebs
    • 1
  • J. R. Perez-Polo
    • 2
  • V. Bigl
    • 1
  1. 1.Department of NeurochemistryPaul Flechsig Institute for Brain ResearchLeipzigFederal Republic of Germany
  2. 2.Department HBC&GUniversity of Texas Medical BranchGalvestonUSA

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