长链酰基辅酶 A 合成酶 4A 调节斑马鱼胚胎中的 Smad 活性和背腹模式形成。
Long-chain Acyl-CoA synthetase 4A regulates Smad activity and dorsoventral patterning in the zebrafish embryo.
机构信息
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
Institute of Developmental Biology, University of Cologne, D-50674 Cologne, Germany.
出版信息
Dev Cell. 2013 Dec 23;27(6):635-47. doi: 10.1016/j.devcel.2013.11.011. Epub 2013 Dec 12.
Long-chain polyunsaturated fatty acids (LC-PUFA) and their metabolites are critical players in cell biology and embryonic development. Here we show that long-chain acyl-CoA synthetase 4a (Acsl4a), an LC-PUFA activating enzyme, is essential for proper patterning of the zebrafish dorsoventral axis. Loss of Acsl4a results in dorsalized embryos due to attenuated bone morphogenetic protein (Bmp) signaling. We demonstrate that Acsl4a modulates the activity of Smad transcription factors, the downstream mediators of Bmp signaling. Acsl4a promotes the inhibition of p38 mitogen-activated protein kinase and the Akt-mediated inhibition of glycogen synthase kinase 3, critical inhibitors of Smad activity. Consequently, introduction of a constitutively active Akt can rescue the dorsalized phenotype of Acsl4a-deficient embryos. Our results reveal a critical role for Acsl4a in modulating Bmp-Smad activity and provide a potential avenue for LC-PUFAs to influence a variety of developmental processes.
长链多不饱和脂肪酸 (LC-PUFA) 及其代谢物是细胞生物学和胚胎发育的关键参与者。在这里，我们表明长链酰基辅酶 A 合成酶 4a (Acsl4a)，一种 LC-PUFA 激活酶，对于斑马鱼背腹轴的正确模式形成是必不可少的。Acsl4a 的缺失导致由于骨形态发生蛋白 (Bmp) 信号减弱而导致背侧化胚胎。我们证明 Acsl4a 调节 Smad 转录因子的活性，Bmp 信号的下游介质。Acsl4a 促进 p38 丝裂原活化蛋白激酶的抑制和 Akt 介导的糖原合酶激酶 3 的抑制，Smad 活性的关键抑制剂。因此，引入组成型活性 Akt 可以挽救 Acsl4a 缺陷胚胎的背侧化表型。我们的结果揭示了 Acsl4a 在调节 Bmp-Smad 活性中的关键作用，并为 LC-PUFAs 影响多种发育过程提供了潜在途径。
Zotero 插件