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A link between very long chain fatty acid elongation and mating-specific yeast cell cycle arrest

机译:非常长链脂肪酸伸长率和交配特异性酵母细胞周期停滞的联系

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摘要

Ceramides and sphingolipid intermediates are well-established regulators of the cell cycle. In the budding yeast Saccharomyces cerevisae, the complex sphingolipid backbone, ceramide, comprises a long chain sphingoid base, a polar head group, and a very long chain fatty acid (VLCFA). While ceramides and long chain bases have been extensively studied as to their roles in regulating cell cycle arrest under multiple conditions, the roles of VLCFAs are not well understood. Here, we used the yeast elo2 and elo3 mutants, which are unable to elongate fatty acids, as tools to explore if maintaining VLCFA elongation is necessary for cell cycle arrest in response to yeast mating. We found that both elo2 and elo3 cells had severely reduced mating efficiencies and were unable to form polarized shmoo projections that are necessary for cell-cell contact during mating. They also lacked functional MAP kinase signaling activity and were defective in initiating a cell cycle arrest in response to pheromone. Additional data suggests that mislocalization of the Ste5 scaffold in elo2 and elo3 mutants upon mating initiation may be responsible for the inability to initiate a cell cycle arrest. Moreover, the lack of proper Ste5 localization may be caused by the inability of mutant cells to mobilize PIP2. We suggest that VLCFAs are required for Ste5 localization, which is a necessary event for initiating MAP kinase signaling and cell cycle arrest during yeast mating initiation.
机译:酰胺和鞘脂中间体是细胞周期的良好稳定的调节剂。在萌芽的酵母酿酒酵母中,复合鞘脂骨架神经酰胺,包括长链鞘氨基底座,极性头部和非常长的链脂肪酸(VLCFA)。虽然神经酰胺和长链基地已经广泛地研究了它们在多种情况下调节细胞周期停滞的作用,但VLCFA的作用也不太了解。在这里,我们使用酵母ELO2和ELO3突变体,其不能伸长脂肪酸,作为探索的工具,如果保持VLCFA伸长率为酵母交配响应酵母交配是必要的。我们发现ELO2和ELO3细胞两者都严重降低了交配效率,并且不能形成在交配期间细胞 - 细胞接触所需的偏振SHMOO突起。它们还缺乏功能性地图激酶信号传导活性,并且在发起响应信息素的细胞周期停留方面有缺陷。附加数据表明,ELO2和ELO3突变体在交配开始时的STE5支架的错误定位可能是不可能启动细胞周期的阻滞。此外,缺乏适当的STE5定位可能是由突变细胞动员PIP2的不可能引起的。我们建议STE5定位需要VLCFA,这是在酵母交配启动期间启动地图激酶信号传导和细胞周期停滞的必要事件。

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