Davies A M, Minichiello L, Klein R
School of Biological and Medical Sciences, University of St Andrews, Fife, UK.
EMBO J. 1995 Sep 15;14(18):4482-9. doi: 10.1002/j.1460-2075.1995.tb00127.x.
Neurotrophins promote neuronal survival by signalling through Trk receptor tyrosine kinases: nerve growth factor signals through TrkA, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)4 through TrkB and NT3 through TrkC. Although studies in some, but not all, cell lines indicate that NT3 can also signal through TrkA and TrkB, it is not known if such signalling can occur in neurons. We show that NT3 can promote the in vitro survival of sensory and sympathetic neurons isolated from embryos that are homozygous for a null mutation in the trkC gene. During the mid-embryonic period, NT3 promoted the survival of as many trigeminal and nodose neurons as the preferred neurotrophins, NGF and BDNF. However, later in development, these neurons lost their ability to respond to NT3. NT3 also promoted the survival of almost all sympathetic neurons, but no decrease in effectiveness was observed during development. Trigeminal neurons from trkC-/- trkA-/- embryos did not respond to NT3 and nodose neurons from trkB-/- embryos likewise failed to respond to NT3. These results show that NT3 can signal through TrkA and TrkB in neurons at certain stages of development and may explain why the phenotype of NT3-/- mice is more severe than that of trkC-/- mice.
神经营养因子通过与Trk受体酪氨酸激酶信号传导来促进神经元存活：神经生长因子通过TrkA信号传导，脑源性神经营养因子（BDNF）和神经营养因子（NT）4通过TrkB信号传导，NT3通过TrkC信号传导。尽管在一些（但不是所有）细胞系中的研究表明NT3也可以通过TrkA和TrkB信号传导，但尚不清楚这种信号传导是否能在神经元中发生。我们发现，NT3可以促进从trkC基因纯合无效突变胚胎中分离出的感觉神经元和交感神经元的体外存活。在胚胎中期，NT3促进三叉神经节和结状神经元存活的数量与首选神经营养因子NGF和BDNF相当。然而，在发育后期，这些神经元失去了对NT3的反应能力。NT3也促进了几乎所有交感神经元的存活，并且在发育过程中未观察到其有效性降低。来自trkC-/- trkA-/-胚胎的三叉神经节神经元对NT3无反应，来自trkB-/-胚胎的结状神经元同样对NT3无反应。这些结果表明，NT3在发育的某些阶段可以通过TrkA和TrkB在神经元中信号传导，这可能解释了为什么NT3-/-小鼠的表型比特rkC-/-小鼠更严重。
