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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The ATP-sensitive potassium (K-ATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman
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The ATP-sensitive potassium (K-ATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman

机译：果蝇心脏功能需要ATP敏感钾（K-ATP）通道编码的dSUR基因，并受tinman调节

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摘要

The homeobox transcription factor Tinman plays an important role in the initiation of heart development. Later functions of Tinman, including the target genes involved in cardiac physiology, are less well studied. We focused on the dSUR gene, which encodes an ATP-binding cassette transmembrane protein that is expressed in the heart. Mammalian SUR genes are associated with K-ATP (ATP-sensitive potassium) channels, which are involved in metabolic homeostasis. We provide experimental evidence that Tinman directly regulates dSUR expression in the developing heart. We identified a cis-regulatory element in the first intron of dSUR, which contains Tinman consensus binding sites and is sufficient for faithful dSUR expression in the fly's myocardium. Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo. Physiological analysis of dSUR knock-down flies supports the idea that dSUR plays a protective role against hypoxic stress and pacing-induced heart failure. Because dSUR expression dramatically decreases with age, it is likely to be a factor involved in the cardiac aging phenotype of Drosophila. dSUR provides a model for addressing how embryonic regulators of myocardial cell commitment can contribute to the establishment and maintenance of cardiac performance.
机译：同源盒转录因子Tinman在心脏发育的起始中起重要作用。 Tinman的后续功能，包括涉及心脏生理的靶基因，尚未得到很好的研究。我们专注于dSUR基因，该基因编码在心脏中表达的ATP结合盒式跨膜蛋白。哺乳动物的SUR基因与K-ATP（ATP敏感性钾）通道相关，后者与代谢稳态有关。我们提供实验证据，证明Tinman直接调节发育中心脏中的dSUR表达。我们在dSUR的第一个内含子中鉴定出一个顺式调控元件，该元件包含Tinman共有结合位点，足以在果蝇的心肌中忠实地表达dSUR。该元素的定点诱变表明，这些Tinman位点对dSUR表达至关重要，进一步的遗传操作表明GATA转录因子Pannier在体内心脏参与的心脏限制性dSUR表达中具有协同作用。 dSUR组合果蝇的生理分析支持以下观点：dSUR对低氧应激和起搏引起的心力衰竭具有保护作用。由于dSUR表达随着年龄的增长而显着降低，这很可能是果蝇心脏衰老表型的一个相关因素。 dSUR提供了一个模型，用于解决心肌细胞定型的胚胎调节剂如何有助于建立和维持心脏功能的问题。

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