Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis
Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis
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DOI：
10.1242/dev.00698
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发表时间：
2003-10-01
期刊：
影响因子：
4.6
通讯作者：
Levin, M
中科院分区：
文献类型：
--
作者：
Bunney, TD;De Boer, AH;Levin, M
为了深入了解胚胎发生过程中 H+ 通量控制形态发生信号的分子机制，我们测试了 Fusicoccin-A (FC)，这是一种由真菌 Fusicoccum amygdali Del 产生的化合物。在植物细胞中，FC 与 14-3-3 蛋白复合，激活 H+ 泵送穿过质膜。长期以来人们一直认为FC只作用于高等植物；在这里，我们表明，在早期发育过程中将青蛙胚胎暴露于 FC 特别会导致左右 (LR) 轴不对称性的随机化（异序性）。生化和分子遗传学证据表明，14-3-3-famfly 蛋白是非洲爪蟾 FC 受体的必然成分，并且 14-3-3 蛋白功能的扰动会导致异位性。 14-3-3 mRNA 和蛋白质的亚细胞定位揭示了新的细胞质目的地，以及第一次细胞分裂时的左右不对称。通过功能获得和功能丧失实验，我们表明 14-3-3E 蛋白可能是 LR 模式的内源性且极其早期的方面。这些数据突显了跨界信号通路的惊人保守性，表明了秀丽隐杆线虫和脊椎动物胚胎之间极性建立的共同机制，并揭示了左右不对称决定通路的新切入点。
To gain insight into the molecular mechanisms underlying the control of morphogenetic signals by H+ flux during embryogenesis, we tested Fusicoccin-A (FC), a compound produced by the fungus Fusicoccum amygdali Del. In plant cells, FC complexes with 14-3-3 proteins to activate H+ pumping across the plasma membrane. It has long been thought that FC acts on higher plants only; here, we show that exposing frog embryos to FC during early development specifically results in randomization of the asymmetry of the left-right (LR) axis (heterotaxia). Biochemical and molecular-genetic evidence is presented that 14-3-3-famfly proteins are an obligate component of Xenopus FC receptors and that perturbation of 14-3-3 protein function results in heterotaxia. The subcellular localization of 14-3-3 mRNAs and proteins reveals novel cytoplasmic destinations, and a left-right asymmetry at the first cell division. Using gain-of-function and loss-of-function experiments, we show that 14-3-3E protein is likely to be an endogenous and extremely early aspect of LR patterning. These data highlight a striking conservation of signaling pathways across kingdoms, suggest common mechanisms of polarity establishment between C. elegans and vertebrate embryos, and uncover a novel entry point into the pathway of left-right asymmetry determination.