Kidane Adhanet H, Heinrich Gerhard, Dirks Ron P H, de Ruyck Brechje A, Lubsen Nicolette H, Roubos Eric W, Jenks Bruce G
Department of Cellular Animal Physiology, Radboud University Nijmegen, Nijmegen, The Netherlands.
Endocrinology. 2009 Mar;150(3):1361-8. doi: 10.1210/en.2008-0993. Epub 2008 Nov 13.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important growth-promoting properties. We report here the first characterization of a BDNF gene in an amphibian, Xenopus laevis, and demonstrate that environmental factors can activate this gene in a promoter-specific fashion. The Xenopus BDNF gene contains six promoter-specific 5'-exons and one 3'-protein-encoding exon. We examined the expression of promoter-specific transcripts in Xenopus neuroendocrine melanotrope cells. These cells make a good model to study how environmental factors control gene expression. In animals placed on a black background melanotrope cells more actively produce and release alphaMSH than in animals on a white background. BDNF is cosequestered and coreleased with alphaMSH and stimulates biosynthesis of proopiomelanocortin (POMC), the precursor protein for alphaMSH. Our analysis of the expression of the BDNF transcripts revealed that there is differential use of some BDNF promoters in melanotrope cells, depending on the adaptation state of the frog. During black-background adaptation, stimulation of expression of BDNF transcript IV preceded that of the POMC transcript, suggesting the BDNF gene is an effector gene for POMC expression. The possible mechanisms regulating expression of the various transcripts are discussed on the basis of the potential calcium- and cAMP-responsive elements in the promoter region of exon IV. Finally, we show that the upstream open reading frames of BDNF transcripts I and IV markedly decrease BDNF translation efficiency, giving the first indication for a functional role of untranslated BDNF exons.
脑源性神经营养因子（BDNF）是一种具有重要促生长特性的神经营养蛋白。我们在此报告了对两栖动物非洲爪蟾中BDNF基因的首次特征描述，并证明环境因素能够以启动子特异性的方式激活该基因。非洲爪蟾的BDNF基因包含六个启动子特异性的5'-外显子和一个3'-蛋白质编码外显子。我们检测了非洲爪蟾神经内分泌黑素细胞中启动子特异性转录本的表达。这些细胞是研究环境因素如何控制基因表达的良好模型。与置于白色背景的动物相比，置于黑色背景的动物的黑素细胞能更活跃地产生和释放α-促黑素细胞激素（αMSH）。BDNF与αMSH共储存并共同释放，刺激阿黑皮素原（POMC）的生物合成，POMC是αMSH的前体蛋白。我们对BDNF转录本表达的分析表明，根据青蛙的适应状态，黑素细胞中某些BDNF启动子的使用存在差异。在黑色背景适应过程中，BDNF转录本IV的表达刺激先于POMC转录本，这表明BDNF基因是POMC表达的效应基因。基于外显子IV启动子区域潜在的钙和环磷酸腺苷反应元件，讨论了调节各种转录本表达的可能机制。最后，我们表明BDNF转录本I和IV的上游开放阅读框显著降低了BDNF的翻译效率，首次表明了未翻译的BDNF外显子的功能作用。
