DEVELOPMENTAL-CHANGES IN NT3 SIGNALING VIA TRKA AND TRKB IN EMBRYONIC NEURONS
DEVELOPMENTAL-CHANGES IN NT3 SIGNALING VIA TRKA AND TRKB IN EMBRYONIC NEURONS
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DOI：
10.1002/j.1460-2075.1995.tb00127.x
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发表时间：
1995-09-15
期刊：
影响因子：
11.4
通讯作者：
KLEIN, R
中科院分区：
文献类型：
--
作者：
DAVIES, AM;MINICHIELLO, L;KLEIN, R
神经营养因子通过Trk受体酪氨酸激酶信号传导促进神经元存活：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，NT 3通过TrkC信号传导。虽然在一些但不是所有细胞系中的研究表明NT 3也可以通过TrkA和TrkB发出信号，但尚不清楚这种信号是否可以在神经元中发生。我们表明，NT 3可以促进感觉和交感神经元的体外存活，这些神经元分离自trkC基因中的无效突变的纯合胚胎。在胚胎中期，NT 3促进了与优选的神经营养因子、NGF和BDNF一样多的三叉神经和结状神经元的存活。然而，在发育后期，这些神经元失去了对NT 3的反应能力，NT 3也促进了几乎所有交感神经元的存活，但在发育过程中没有观察到有效性降低。来自trkC（-/-）trkA（-/-）胚胎的三叉神经元对NT 3没有反应，来自trkB（-/-）胚胎的结状神经元同样对NT 3没有反应。这些结果表明，NT 3可以通过神经元中的TrkA和TrkB在某些发育阶段进行信号传导，并且可以解释为什么NT 3（-/-）小鼠的表型比trkC（-/-）小鼠的表型更严重。
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.