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Characterization of a Distinctive Motif of the Low Molecular Weight Neurotrophin Receptor that Modulates NGF‐mediated Neurite Growth
Author(s) -
Dostaler S. M.,
Ross G. M.,
Myers S. M.,
Weaver D. F.,
Ananthanarayanan V.,
Riopelle R. J.
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01574.x
Subject(s) - neurite , tropomyosin receptor kinase a , nerve growth factor , neurotrophin , microbiology and biotechnology , peptide , growth cone , receptor , biology , chemistry , low affinity nerve growth factor receptor , biochemistry , in vitro , axon
The cytoplasmic region of the common neurotrophin receptor (p75 NGFR ) (rat, human, chick) contains a putative membrane‐associating domain implicated in intracellular signalling. A peptide (R3) identical to this domain (p75 NGFR 367–379) and various analogues of this peptide displayed circular dichroism spectra in aqueous and non‐polar environments identical to the amphiphilic tetradecapeptide mastoparan (MP) and were internalized by PC12 rat pheochromocytoma cells. The R3 peptide enhanced neurite growth in PC12 cells, embryo chick primary sensory neurons and fetal rat primary sensory neurons in vitro in the presence of sub‐saturating concentrations of NGF. Peptide analogues of R3 not faithful to the distance and angular relationships of ionic groups and the putative amphiphilic structure of p75 NGFR 367–379 displayed reduced potency to enhance NGF‐mediated neurite growth. Exposure of NGF and the R3 peptide to a cell line displaying predominantly p75 NGFR (PC12 nnr5 ), had no influence on neurite growth. The R3 peptide had no effects on cell survival, cell binding or uptake of [ 125 I]NGF, affinity cross‐linking of [ 125 I]NGF to p75 NGFR or trkA monomers and homodimers, or NGF‐mediated trkA monomer tyrosine phosphorylation. The studies implicate a role for a highly conserved motif of p75 NGFR in the downstream modulation of NGF‐mediated neurite growth.