Expression and function of TrkB variants in developing sensory neurons
Expression and function of TrkB variants in developing sensory neurons
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DOI：
10.1002/j.1460-2075.1996.tb01029.x
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发表时间：
1996-12-02
期刊：
影响因子：
11.4
通讯作者：
Davies, AM
中科院分区：
文献类型：
--
作者：
Ninkina, N;Adu, J;Davies, AM
小鼠三叉神经元在其轴突生长到其靶点时独立于神经营养因子存活，然后在成为神经营养因子依赖性之前被BDNF短暂支持。在神经营养因子不依赖性阶段，编码BDNF受体TrkB的转录物以非常低的水平表达，在BDNF依赖性阶段，高水平表达编码具有催化酪氨酸激酶结构域的受体的转录物，虽然该转录物的水平随着神经元失去对BDNF的响应性而下降，但编码缺乏激酶结构域的TrkB变体的转录物的表达伴随增加。对来自纯化的神经元的RNA的分析表明，所有这些转录物都存在于神经元中，脑源性神经营养因子和神经生长因子上升-TrkB在发育早期调节这些转录本的表达，但后来几乎没有影响。TrkB，我们将TrkB表达质粒注射到NGF依赖的交感神经元中。而催化TrkB单独表达赋予BDNF存活反应，非催化TrkB的共表达实质上降低了这种反应。我们的研究结果表明，在发展过程中的感觉神经元BDNF的反应是由催化和非催化TrkB的相对水平调制。
Mouse trigeminal neurons survive independently of neurotrophins when their axons are growing to their targets, and are then transiently supported by BDNF before becoming NGF dependent, During the stage of neurotrophin independence, transcripts encoding the BDNF receptor, TrkB, were expressed at very low levels, During the stage of BDNF dependence, high levels of a transcript encoding a receptor with the catalytic tyrosine kinase domain were expressed, Although the levels of this transcript fell as the neurons lost responsiveness to BDNF, there were concomitant increases in the expression of transcripts encoding TrkB variants lacking the kinase domain, Analysis of RNA from purified neurons showed that all of these transcripts were present in neurons, BDNF and NGF up-regulated the expression of these transcripts early in development but had little effect later on. To test whether truncated TrkB modulates BDNF signalling via catalytic TrkB, we injected TrkB expression plasmids into NGF-dependent sympathetic neurons. Whereas expression of catalytic TrkB alone conferred a BDNF survival response, co-expression of non-catalytic TrkB substantially reduced this response. Our results suggest that BDNF responsiveness in sensory neurons during development is modulated by the relative levels of catalytic and non-catalytic TrkB.