Characterization of a distinctive motif of the low molecular weight neurotrophin receptor that modulates NGF-mediated neurite growth.
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 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]NGF, affinity cross-linking of [125]NGF to p75(NGFR) or trkA monomers and homodimers, of 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.
Dostaler
S M
SM
Department of Medicine, Queen's University, Kingston, Ontario, Canada K7L 2V7.
Ross
G M
GM
Myers
S M
SM
Weaver
D F
DF
Ananthanarayanan
V
V
Riopelle
R J
RJ
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D019070:Cell Lineage; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000648:ultrastructure*; D009479:Neuropeptides / Q000494:pharmacology; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000096:biosynthesis; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry*; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009414:Nerve Growth Factors; D009479:Neuropeptides; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D010566:Virulence Factors, Bordetella; D020917:Receptor, trkA; D008274:Magnesium