Expression of the neurotirophin receptor trkB is regulated by the cAMP/CREB pathway in neurons
Expression of the neurotirophin receptor trkB is regulated by the cAMP/CREB pathway in neurons
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DOI：
10.1016/j.mcn.2004.03.007
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Rodríguez-Peña, A
中科院分区：
文献类型：
--
作者：
Deogracias, R;Espliguero, G;Rodríguez-Peña, A
脑源性神经营养因子（BDNF）/神经营养因子（NT）-4/5作为神经营养因子的受体，在成人脑的发育、维持及其对损伤或病理条件的适应中起着至关重要的作用。尽管如此，很少有人知道的机制，调节其表达。在这里，我们表明，毛喉素（FK）迅速刺激表达的全长和截断trkB亚型在原代培养的皮层神经元。凝胶迁移分析和瞬时转染实验表明，这种激活发生通过蛋白激酶A（PKA）/环AMP反应元件结合蛋白（CREB）依赖性机制。活化的CREB结合到位于trkB基因的P2启动子内的两个CRE位点的第二个环AMP（cAMP）响应元件（CRE），其能够赋予cAMP对异源启动子的响应性。我们的研究结果表明，trkB基因是CREB调控的目标，并解释了在CREB参与的神经系统的不同适应性反应中产生的trkB表达的增加。(C)2004年爱思唯尔公司All rights reserved.
trkB as receptor for neurotrophins brain-derived neurotrophic factor (BDNF)/neurotrophin (NT)-4/5 plays a crucial role during development, maintenance of the adult brain, and its adaptation to injury or pathological conditions. In spite of this, very little is known about the mechanisms that regulate its expression. Here, we show that forskolin (Fk) rapidly stimulates the expression of both the full-length and truncated trkB isoforms in primary cultures of cortical neurons. Gel shift assays and transient transfection experiments demonstrate that this activation occurs via a protein kinase A (PKA)/cyclic AMP-responsive element-binding protein (CREB)-dependent mechanism. Activated CREB binds to the second cyclic AMP (cAMP)-responsive element (CRE) of the two CRE sites located within the P2 promoter of the trkB gene, which is able to confer cAMP responsiveness to a heterologous promoter. Our results illustrate that the trkB gene is a target for CREB regulation and explain the increase of trkB expression produced in different adaptative responses of the nervous system where CREB is participating. (C) 2004 Elsevier Inc. All rights reserved.