Modulating composition and shape of biological membranes is an emerging mode of regulation of cellular processes. We investigated the global effects that such perturbations have on a model eukaryotic cell. Phospholipases A(2) (PLA(2)s), enzymes that cleave one fatty acid molecule from membrane phospholipids, exert their biological activities through affecting both membrane composition and shape. We have conducted a genome-wide analysis of cellular effects of a PLA(2) in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA(2) activity and the Rim101 signaling pathway in S. cerevisiae. Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway. We describe a genetically and functionally related network, consisting of components of the Rim101 pathway and the prefoldin, retromer and SWR1 complexes, and predict its functional relation to PLA(2) activity in a model eukaryotic cell. This study provides a list of the players involved in the global response to changes in membrane composition and shape in a model eukaryotic cell, and further studies are needed to understand the precise molecular mechanisms connecting them.

译文

:调节生物膜的组成和形状是调节细胞过程的一种新兴模式。我们研究了这种扰动对模型真核细胞的整体影响。磷脂酶A(2)(PLA(2)s)是一种从膜磷脂上切割一个脂肪酸分子的酶,通过影响膜的组成和形状来发挥其生物学活性。我们已经进行了全基因组范围内的酿酒酵母作为模型系统的PLA(2)的细胞作用的分析。我们展示了功能基因和生化相互作用之间的PLA(2)活动和啤酒酵母Rim101信号通路。我们的结果表明,内体膜的组成和/或形状会影响Rim101途径。我们描述了一个遗传和功能相关的网络,由Rim101途径和prefoldin,Retromer和SWR1复合物的组成组成,并预测其对模型真核细胞中PLA(2)活性的功能关系。这项研究提供了参与对真核细胞模型中膜组成和形状变化的整体反应的参与者的清单,还需要进一步的研究来了解连接它们的精确分子机制。

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