Conover J C, Erickson J T, Katz D M, Bianchi L M, Poueymirou W T, McClain J, Pan L, Helgren M, Ip N Y, Boland P
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Nature. 1995 May 18;375(6528):235-8. doi: 10.1038/375235a0.
Nerve growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases. TrkB is relatively promiscuous in vitro, acting as a receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT4) and, to a lesser extent, NT3 (refs 3-5). Mice lacking TrkB show a more severe phenotype than mice lacking BDNF, suggesting that TrkB may act as a receptor for additional ligands in vivo. To explore this possibility, we generated mice lacking NT4 or BDNF as well as mice lacking both neurotrophins. Unlike mice lacking other Trks or neurotrophins, NT4-deficient mice are long-lived and show no obvious neurological defects. Analysis of mutant phenotypes revealed distinct neuronal populations with different neurotrophin requirements. Thus vestibular and trigeminal sensory neurons require BDNF but not NT4, whereas nodose-petrosal sensory neurons require both BDNF and NT4. Motor neurons, whose numbers are drastically reduced in mice lacking TrkB, are not affected even in mice lacking both BDNF and NT4. These results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo.
神经生长因子和其他神经营养因子通过受体酪氨酸激酶Trk家族向神经元发出信号。TrkB在体外相对不专一，可作为脑源性神经营养因子（BDNF）、神经营养因子-4（NT4）的受体，在较小程度上还可作为NT3的受体（参考文献3 - 5）。缺乏TrkB的小鼠表现出比缺乏BDNF的小鼠更严重的表型，这表明TrkB在体内可能作为其他配体的受体。为了探究这种可能性，我们培育出了缺乏NT4或BDNF的小鼠以及同时缺乏这两种神经营养因子的小鼠。与缺乏其他Trk或神经营养因子的小鼠不同，缺乏NT4的小鼠寿命长且没有明显的神经缺陷。对突变体表型的分析揭示了具有不同神经营养因子需求的不同神经元群体。因此，前庭和三叉神经感觉神经元需要BDNF而不是NT4，而结状 - 岩神经节感觉神经元则同时需要BDNF和NT4。运动神经元在缺乏TrkB的小鼠中数量大幅减少，但即使在同时缺乏BDNF和NT4的小鼠中也不受影响。这些结果表明，另一种配体，可能是NT3，确实在体内作用于TrkB。
