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

Neurobiology of Disease

Stephen Brimijoin¹  Laurence J. Miller²  Anthony J. Windebank³  Anna M. Conti³ 

[1] Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, College of Medicine, Rochester, MN 55905, USA;Division of Gastroenterology and Hepatology and Internal Medicine, Mayo Clinic, College of Medicine, Scottsdale, AZ 82224, USA;Department of Neurology, Mayo Clinic, College of Medicine, Rochester, MN 55905, USA;

关键词: Neurite outgrowth;    Nerve growth factor;    p75NTR receptors;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown