Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons
Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons
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DOI：
10.1016/s0092-8674(03)00390-8
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发表时间：
2003-05-30
期刊：
影响因子：
64.5
通讯作者：
Crabtree, GR
中科院分区：
文献类型：
--
作者：
Graef, IA;Wang, F;Crabtree, GR
轴突生长是神经元连接形成的第一步，但调节轴突延伸的途径仍然知之甚少。我们发现缺乏钙调神经磷酸酶-NFAT信号传导的小鼠在轴突生长方面存在显着缺陷，但在神经元分化或存活方面几乎没有或没有缺陷。在体外，缺乏钙调神经磷酸酶功能或 NFATc2、c3 和 c4 的感觉和连合神经元无法对神经营养素或 netrin-1 作出反应并有效地轴突生长。神经营养蛋白和神经蛋白刺激 NFATc4 的钙调神经磷酸酶依赖性核定位，并激活培养的原代神经元中 NFAT 介导的基因转录。这些数据表明，这些胚胎轴突对生长因子做出反应并快速生长的能力需要这些因子激活钙调神经磷酸酶/NFAT 信号传导。精确解析伸长转向和存活的信号可以允许在发育过程中独立控制这些过程。
Axon outgrowth is the first step in the formation of neuronal connections, but the pathways that regulate axon extension are still poorly understood. We find that mice deficient in calcineurin-NFAT signaling have dramatic defects in axonal outgrowth, yet have little or no defect in neuronal differentiation or survival. In vitro, sensory and commissural neurons lacking calcineurin function or NFATc2, c3, and c4 are unable to respond to neurotrophins or netrin-1 with efficient axonal outgrowth. Neurotrophins and netrins stimulate calcineurin-dependent nuclear localization of NFATc4 and activation of NFAT-mediated gene transcription in cultured primary neurons. These data indicate that the ability of these embryonic axons to respond to growth factors with rapid outgrowth requires activation of calcineurin/NFAT signaling by these factors. The precise parsing of signals for elongation turning and survival could allow independent control of these processes during development.