Tian Tianhai, Harding Angus, Inder Kerry, Plowman Sarah, Parton Robert G, Hancock John F
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia.
Nat Cell Biol. 2007 Aug;9(8):905-14. doi: 10.1038/ncb1615. Epub 2007 Jul 8.
Ras proteins occupy dynamic plasma membrane nanodomains called nanoclusters. The significance of this spatial organization is unknown. Here we show, using in silico and in vivo analyses of mitogen-activated protein (MAP) kinase signalling, that Ras nanoclusters operate as sensitive switches, converting graded ligand inputs into fixed outputs of activated extracellular signal-regulated kinase (ERK). By generating Ras nanoclusters in direct proportion to ligand input, cells build an analogue-digital-analogue circuit relay that transmits a signal across the plasma membrane with high fidelity. Signal transmission is completely dependent on Ras spatial organization and fails if nanoclustering is abrogated. A requirement for high-fidelity signalling may explain the non-random distribution of other plasma membrane signalling complexes.
Ras蛋白定位于称为纳米簇的动态质膜纳米结构域。这种空间组织的意义尚不清楚。在这里，我们通过对丝裂原活化蛋白（MAP）激酶信号传导进行计算机模拟和体内分析表明，Ras纳米簇作为敏感开关，将分级配体输入转化为活化的细胞外信号调节激酶（ERK）的固定输出。通过与配体输入成正比地生成Ras纳米簇，细胞构建了一个模拟-数字-模拟电路中继，以高保真度跨质膜传输信号。信号传输完全依赖于Ras的空间组织，如果纳米簇形成被消除则信号传输失败。对高保真信号传导的需求可能解释了其他质膜信号复合物的非随机分布。
