Dostaler S M, Ross G M, Myers S M, Weaver D F, Ananthanarayanan V, Riopelle R J
Department of Medicine, Queen's University, Kingston, Ontario, Canada K7L 2V7.
Eur J Neurosci. 1996 May;8(5):870-9. doi: 10.1111/j.1460-9568.1996.tb01574.x.
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.
常见神经营养因子受体（p75(NGFR)）（大鼠、人类、鸡）的胞质区域包含一个与细胞内信号传导相关的假定膜结合结构域。一种与该结构域相同的肽（R3）（p75(NGFR) 367 - 379）及其各种类似物在水性和非极性环境中显示出与两亲性十四肽马斯托帕兰（MP）相同的圆二色光谱，并被PC12大鼠嗜铬细胞瘤细胞内化。在亚饱和浓度的神经生长因子（NGF）存在下，R3肽在体外增强了PC12细胞、鸡胚初级感觉神经元和胎鼠初级感觉神经元的神经突生长。不忠实于离子基团的距离和角度关系以及p75(NGFR)367 - 379假定两亲结构的R3肽类似物显示出增强p75(NGFR)（PC12(nnr5)）的效力降低，对神经突生长没有影响。R3肽对细胞存活、细胞结合或[125]NGF的摄取、[125]NGF与p75(NGFR)或trkA单体及同二聚体的亲和交联、NGF介导的trkA单体酪氨酸磷酸化均无影响。这些研究表明p75(NGFR)的一个高度保守基序在NGF介导的神经突生长的下游调节中起作用。
