Ninkina N, Adu J, Fischer A, Piñón L G, Buchman V L, Davies A M
School of Biological and Medical Sciences, University of St Andrews, UK.
EMBO J. 1996 Dec 2;15(23):6385-93.
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.
小鼠三叉神经元在其轴突向靶标生长时可独立于神经营养因子存活，然后在变得依赖神经生长因子（NGF）之前由脑源性神经营养因子（BDNF）短暂支持。在神经营养因子非依赖阶段，编码BDNF受体TrkB的转录本表达水平非常低。在BDNF依赖阶段，编码具有催化酪氨酸激酶结构域的受体的转录本高水平表达。尽管随着神经元对BDNF失去反应性，该转录本水平下降，但编码缺乏激酶结构域的TrkB变体的转录本表达却随之增加。对纯化神经元的RNA分析表明，所有这些转录本都存在于神经元中。BDNF和NGF在发育早期上调这些转录本的表达，但后期影响很小。为了测试截短的TrkB是否通过催化性TrkB调节BDNF信号传导，我们将TrkB表达质粒注入依赖NGF的交感神经元。单独表达催化性TrkB可赋予BDNF存活反应，而非催化性TrkB的共表达则大大降低了这种反应。我们的结果表明，发育过程中感觉神经元对BDNF的反应性受催化性和非催化性TrkB相对水平的调节。
