Neurotrophins induce release of neurotrophins by the regulated secretory pathway
Neurotrophins induce release of neurotrophins by the regulated secretory pathway
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DOI：
10.1073/pnas.95.16.9614
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Shooter, EM
中科院分区：
文献类型：
--
作者：
Krüttgen, A;Möller, JC;Shooter, EM
最近的研究已经确定，神经营养因子的合成和分泌受活动的调节，并且这些因子参与神经系统中的活动依赖性过程。神经营养因子也已知诱导细胞内钙的增加，这是调节分泌的触发因素。这一发现增加了神经营养因子本身刺激神经营养因子分泌的可能性。为了解决这个问题，我们研究了从转染的PC 12细胞，一个广泛使用的模型神经分泌和神经营养因子信号转导的神经营养因子的释放。我们发现，神经营养素诱导脑源性神经营养因子，神经营养素-3（NT-3）和神经营养素-4/5的分泌调节。脑源性神经营养因子对NT-3释放的影响可被p75阻断抗体雷克斯所消除，但不能被神经营养因子酪氨酸激酶受体（Trk）信号通路抑制剂K252 a所消除。同时应用雷克斯和K252 a可以阻断神经生长因子对NT-3释放的影响，表明它们是由TrkA和p75介导的。我们的数据表明，神经营养因子能够诱导神经营养因子的调节分泌，并表明TrkA和p75在这个过程中起信号转导作用。神经营养因子诱导的神经营养因子释放可能与活动依赖性过程相关，如突触可塑性和记忆形成。
Recent studies have established that neurotrophin synthesis and secretion are regulated by activity and that these factors are involved in activity-dependent processes in the nervous system. Neurotrophins also are known to induce increases in intracellular calcium, a trigger for regulated secretion. This finding raises the possibility that neurotrophins themselves mag stimulate regulated secretion of neurotrophins. To address this question, we studied the release of neurotrophins from transfected PC12 cells, a widely used model for neuronal secretion and neurotrophin signal transduction. We found that neurotrophins induced the regulated secretion of brain-derived neurotrophic factor, neurotrophin-3 (NT-3, and neurotrophin-4/5. The effect of brain-derived neurotrophic factor on release of NT-3 could be abolished by REX, a p75 blocking antibody, but not by K252a, an inhibitor of neurotrophin tyrosine kinase receptor (Trk) signaling. The nerve growth factor effect on release of NT-3 could be blocked only by simultaneous application of REX and K252a, suggesting that they are mediated by TrkA as well as p75, Our data show that neurotrophins are able to induce the regulated secretion of neurotrophins and suggest a signal-transducing role for both TrkA and p75 in this process. The neurotrophin-induced release of neurotrophins may be relevant for activity-dependent processes such as synaptic plasticity and memory formation.