THE P75 NERVE GROWTH-FACTOR RECEPTOR MEDIATES SURVIVAL OR DEATH DEPENDING ON THE STAGE OF SENSORY NEURON DEVELOPMENT
THE P75 NERVE GROWTH-FACTOR RECEPTOR MEDIATES SURVIVAL OR DEATH DEPENDING ON THE STAGE OF SENSORY NEURON DEVELOPMENT
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DOI：
10.1073/pnas.91.14.6501
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发表时间：
1994-07-05
影响因子：
11.1
通讯作者：
BARTLETT, PF
中科院分区：
文献类型：
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作者：
BARRETT, GL;BARTLETT, PF
低亲和力神经生长因子（NGF）受体p75（NGFR）在发育过程中调节神经元存活的功能尚不清楚。突变的p75（NGFR）小鼠的感觉缺陷表明，它是必要的感觉神经元的发展，然而，是否需要，除了trkA，信号转导或更多地参与定位的神经生长因子尚未解决。在这项研究中，我们证明，在体外，降低水平的p75（NGFR）的表达在感觉神经元的反义寡核苷酸在很大程度上防止了神经生长因子介导的存活的感觉神经元从胚胎第12天和第15天的小鼠，但增加了存活的胚胎第19天和出生后第2天的感觉神经元在没有神经生长因子。因此，p75（NGFR）是目标神经支配阶段神经元中NGF介导的存活所需的，但可以在细胞发育的后期介导凋亡信号，因此，p75（NGFR）在围产期经历功能转换：在胚胎发生过程中，可能需要trkA在NGF存在下介导神经元存活，但在出生后早期，在缺乏NGF的情况下，它充当组成性死亡信号。
The function of the low-affinity nerve growth factor (NGF) receptor, p75(NGFR), in regulating neuronal survival during development is unclear. The sensory deficit in mice with mutated p75(NGFR) suggests it is necessary for development of sensory neurons; however, whether it is required, in addition to trkA, for signal transduction or is more involved in localization of NGF is unresolved. In this study we demonstrate, in vitro, that lowering the levels of p75(NGFR) expression in sensory neurons with antisense oligonucleotides largely prevents the NGF-mediated survival of sensory neurons from embryonic day 12 and 15 mice but increases the survival of embryonic day 19 and postnatal day 2 sensory neurons in the absence of NGF. Thus, the p75(NGFR) is, required for NGF-mediated survival in neurons at the stage of target innervation but can mediate an apoptotic signal at a later stage of cell development, Thus, p75(NGFR) undergoes a switch in function in the perinatal period: during embryogenesis it is required, probably with trkA, to mediate neuronal survival in the presence of NGF, but in the early postnatal period it acts as a constitutive death signal in the absence of NGF.