APP regulates NGF receptor trafficking and NGF-mediated neuronal differentiation and survival

Yun Wu Zhang, Yaomin Chen, Yun Liu, Yingjun Zhao, Francesca-Fang Liao, Huaxi Xu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

β-amyloid precursor protein (APP) is a key factor in Alzheimer's disease (AD) but its physiological function is largely undetermined. APP has been found to regulate retrograde transport of nerve growth factor (NGF), which plays a crucial role in mediating neuronal survival and differentiation. Herein, we reveal the mechanism underlying APP-mediated NGF trafficking, by demonstrating a direct interaction between APP and the two NGF receptors, TrkA and p75NTR. Downregulation of APP leads to reduced cell surface levels of TrkA/p75NTR and increased endocytosis of TrkA/p75NTR and NGF. In addition, APP-deficient cells manifest defects in neurite outgrowth and are more susceptible to Aβ-induced neuronal death at physiological levels of NGF. However, APP-deficient cells show better responses to NGF-stimulated differentiation and survival than control cells. This may be attributed to increased receptor endocytosis and enhanced activation of Akt and MAPK upon NGF stimulation in APP-deficient cells. Together, our results suggest that APP mediates endocytosis of NGF receptors through direct interaction, thereby regulating endocytosis of NGF and NGF-induced downstream signaling pathways for neuronal survival and differentiation.

Original languageEnglish (US)
Article numbere80571
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 1 2013

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Nerve Growth Factor Receptor
nerve growth factor
Amyloid beta-Protein Precursor
Nerve Growth Factor
amyloid
receptors
Endocytosis
endocytosis
proteins
Nerve Growth Factor Receptors
cells
neurites
Alzheimer disease
Cell Survival
Alzheimer Disease
Down-Regulation
Chemical activation
death
Defects

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

APP regulates NGF receptor trafficking and NGF-mediated neuronal differentiation and survival. / Zhang, Yun Wu; Chen, Yaomin; Liu, Yun; Zhao, Yingjun; Liao, Francesca-Fang; Xu, Huaxi.

In: PloS one, Vol. 8, No. 11, e80571, 01.11.2013.

Research output: Contribution to journalArticle

Zhang, Yun Wu ; Chen, Yaomin ; Liu, Yun ; Zhao, Yingjun ; Liao, Francesca-Fang ; Xu, Huaxi. / APP regulates NGF receptor trafficking and NGF-mediated neuronal differentiation and survival. In: PloS one. 2013 ; Vol. 8, No. 11.
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