Characterization of a distinctive motif of the low molecular weight neurotrophin receptor that modulates NGF-mediated neurite growth

被引:14
作者
Dostaler, SM
Ross, GM
Myers, SM
Weaver, DF
Ananthanarayanan, V
Riopelle, RJ
机构
[1] QUEENS UNIV,DEPT MED,KINGSTON,ON K7L 2V7,CANADA
[2] MCMASTER UNIV,DEPT BIOCHEM,HAMILTON,ON L8N 3Z5,CANADA
关键词
neurite growth; p75; neurotrophin; signalling;
D O I
10.1111/j.1460-9568.1996.tb01574.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 [I-125]NGF, affinity cross-linking of [I-125]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.
引用
收藏
页码:870 / 879
页数:10
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