Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not
Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not
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DOI：
10.1038/nature09336
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发表时间：
2010-09-02
期刊：
影响因子：
64.8
通讯作者：
Barde, Yves-Alain
中科院分区：
文献类型：
--
作者：
Nikoletopoulou, Vassiliki;Lickert, Heiko;Barde, Yves-Alain
周围神经系统的神经元长期以来一直被认为需要生存因子来防止它们在发育期间死亡。但是，为什么它们选择性地依赖于分泌分子仍然是一个谜，因为在中枢神经系统中，大多数神经元并没有表现出这种依赖性。使用工程胚胎干细胞，我们在这里显示，神经营养因子受体TrkA和TrkC（原肌球蛋白受体激酶A和C，也被称为Ntrk1和Ntrk3，分别）指示发育中的神经元死亡，在体外和体内。相比之下，TrkB（也称为Ntrk2），一种主要在中枢神经系统中表达的密切相关的受体，却没有。这些结果表明，TrkA和TrkC的行为依赖受体，解释了为什么发展中的交感神经元和感觉神经元成为营养因子依赖的生存。我们认为，扩展的Trk基因家族，伴随着从中枢神经系统的外围隔离产生了一种新的细胞数量控制机制。
Neurons of the peripheral nervous system have long been known to require survival factors to prevent their death during development. But why they selectively become dependent on secretory molecules has remained a mystery, as is the observation that in the central nervous system, most neurons do not show this dependency. Using engineered embryonic stem cells, we show here that the neurotrophin receptors TrkA and TrkC (tropomyosin receptor kinase A and C, also known as Ntrk1 and Ntrk3, respectively) instruct developing neurons to die, both in vitro and in vivo. By contrast, TrkB (also known as Ntrk2), a closely related receptor primarily expressed in the central nervous system, does not. These results indicate that TrkA and TrkC behave as dependence receptors, explaining why developing sympathetic and sensory neurons become trophic-factor-dependent for survival. We suggest that the expansion of the Trk gene family that accompanied the segregation of the peripheral from the central nervous system generated a novel mechanism of cell number control.