Suppression of neurite outgrowth by high-dose nerve growth factor is independent of functional p75NTR receptors

Anna M. Conti; Stephen Brimijoin; Laurence J. Miller; Anthony J. Windebank

doi:10.1016/j.nbd.2003.09.009

Suppression of neurite outgrowth by high-dose nerve growth factor is independent of functional p75NTR receptors

Anna M. Conti, Stephen Brimijoin, Laurence J. Miller, Anthony J. Windebank

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

19 Scopus citations

Abstract

We have previously demonstrated that high concentrations of nerve growth factor suppress neurite outgrowth from sensory neurons. Inhibition could be mediated by either the p75NTR or TrkA receptor. We used a functional block of p75NTR by REX antibody in rat dorsal root ganglion neurons and dorsal root ganglion cultures from p75NTR knockout mice. In both systems, high-dose NGF inhibited neurite outgrowth, implying that p75NTR is not involved in suppression of neurite outgrowth. Confocal images of dissociated dorsal root ganglion neurons exposed to fluorescence-tagged NGF showed ligand internalization. Radioligand binding indicated disappearance of high-affinity binding sites from the surface of dorsal root ganglia after treatment with 200 ng/ml NGF for 1 h. Downstream signaling showed sustained hyperphosphorylation of MAPK (Erk_1-2) but not of SNT or Akt. High-dose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR.

Original language	English (US)
Pages (from-to)	106-114
Number of pages	9
Journal	Neurobiology of Disease
Volume	15
Issue number	1
DOIs	https://doi.org/10.1016/j.nbd.2003.09.009
State	Published - Feb 2004

Keywords

Nerve growth factor
Neurite outgrowth
p75NTR receptors

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2003.09.009

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title = "Suppression of neurite outgrowth by high-dose nerve growth factor is independent of functional p75NTR receptors",

abstract = "We have previously demonstrated that high concentrations of nerve growth factor suppress neurite outgrowth from sensory neurons. Inhibition could be mediated by either the p75NTR or TrkA receptor. We used a functional block of p75NTR by REX antibody in rat dorsal root ganglion neurons and dorsal root ganglion cultures from p75NTR knockout mice. In both systems, high-dose NGF inhibited neurite outgrowth, implying that p75NTR is not involved in suppression of neurite outgrowth. Confocal images of dissociated dorsal root ganglion neurons exposed to fluorescence-tagged NGF showed ligand internalization. Radioligand binding indicated disappearance of high-affinity binding sites from the surface of dorsal root ganglia after treatment with 200 ng/ml NGF for 1 h. Downstream signaling showed sustained hyperphosphorylation of MAPK (Erk1-2) but not of SNT or Akt. High-dose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR.",

keywords = "Nerve growth factor, Neurite outgrowth, p75NTR receptors",

author = "Conti, {Anna M.} and Stephen Brimijoin and Miller, {Laurence J.} and Windebank, {Anthony J.}",

note = "Funding Information: This work was supported by National Institutes of Health grant NS 40471. We are grateful to Ms. Elizabeth M. Hadac and Ms. Susan M. Kuntz for excellent advice in binding techniques and to Mr. James E. Tarara for assistance in the Optical Morphology Core Laboratory. ",

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language = "English (US)",

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AU - Brimijoin, Stephen

AU - Miller, Laurence J.

AU - Windebank, Anthony J.

N1 - Funding Information: This work was supported by National Institutes of Health grant NS 40471. We are grateful to Ms. Elizabeth M. Hadac and Ms. Susan M. Kuntz for excellent advice in binding techniques and to Mr. James E. Tarara for assistance in the Optical Morphology Core Laboratory.

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N2 - We have previously demonstrated that high concentrations of nerve growth factor suppress neurite outgrowth from sensory neurons. Inhibition could be mediated by either the p75NTR or TrkA receptor. We used a functional block of p75NTR by REX antibody in rat dorsal root ganglion neurons and dorsal root ganglion cultures from p75NTR knockout mice. In both systems, high-dose NGF inhibited neurite outgrowth, implying that p75NTR is not involved in suppression of neurite outgrowth. Confocal images of dissociated dorsal root ganglion neurons exposed to fluorescence-tagged NGF showed ligand internalization. Radioligand binding indicated disappearance of high-affinity binding sites from the surface of dorsal root ganglia after treatment with 200 ng/ml NGF for 1 h. Downstream signaling showed sustained hyperphosphorylation of MAPK (Erk1-2) but not of SNT or Akt. High-dose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR.

AB - We have previously demonstrated that high concentrations of nerve growth factor suppress neurite outgrowth from sensory neurons. Inhibition could be mediated by either the p75NTR or TrkA receptor. We used a functional block of p75NTR by REX antibody in rat dorsal root ganglion neurons and dorsal root ganglion cultures from p75NTR knockout mice. In both systems, high-dose NGF inhibited neurite outgrowth, implying that p75NTR is not involved in suppression of neurite outgrowth. Confocal images of dissociated dorsal root ganglion neurons exposed to fluorescence-tagged NGF showed ligand internalization. Radioligand binding indicated disappearance of high-affinity binding sites from the surface of dorsal root ganglia after treatment with 200 ng/ml NGF for 1 h. Downstream signaling showed sustained hyperphosphorylation of MAPK (Erk1-2) but not of SNT or Akt. High-dose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR.

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Suppression of neurite outgrowth by high-dose nerve growth factor is independent of functional p75NTR receptors

Abstract

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