Incoherent feedforward control governs adaptation of activated ras in a eukaryotic chemotaxis pathway.
Incoherent feedforward control governs adaptation of activated ras in a eukaryotic chemotaxis pathway.
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DOI：
10.1126/scisignal.2002413
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发表时间：
2012-01-03
影响因子：
7.3
通讯作者：
Firtel RA
中科院分区：
文献类型：
--
作者：
Takeda K;Shao D;Adler M;Charest PG;Loomis WF;Levine H;Groisman A;Rappel WJ;Firtel RA
信号系统的适应过程中，输入变化后输出返回到固定基线，通常涉及负反馈循环，并在真核趋化性中发挥至关重要的作用。我们确定了紧邻 G 蛋白偶联受体下游的真核趋化途径的趋化剂浓度均匀变化的动态响应。激活的 Ras 的响应表现出近乎完美的适应，导致我们尝试使用数学模型来拟合两种可能的简单网络拓扑的结果，以提供完美的适应。只有非相干前馈网络准确地描述了实验结果。该分析表明，该 Ras 途径的适应是通过上游组件的成比例激活而不是通过负反馈循环来实现的。此外，这些结果与梯度传感的局部激发、全局抑制机制一致，可能是 Ras 鸟苷三磷酸酶激活蛋白充当全局抑制剂。
Adaptation in signaling systems, during which the output returns to a fixed baseline after a change in the input, often involves negative feedback loops and plays a crucial role in eukaryotic chemotaxis. We determined the dynamical response to a uniform change in chemoattractant concentration of a eukaryotic chemotaxis pathway immediately downstream from G protein–coupled receptors. The response of an activated Ras showed near-perfect adaptation, leading us to attempt to fit the results using mathematical models for the two possible simple network topologies that can provide perfect adaptation. Only the incoherent feedforward network accurately described the experimental results. This analysis revealed that adaptation in this Ras pathway is achieved through the proportional activation of upstream components and not through negative feedback loops. Furthermore, these results are consistent with a local excitation, global inhibition mechanism for gradient sensing, possibly with a Ras guanosine triphosphatase–activating protein acting as a global inhibitor.
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影响因子：
64.8
作者：
Barkai, N;Leibler, S
通讯作者：
Leibler, S
DOI：
10.1073/pnas.0601302103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Levine, Herbert;Kessler, David A.;Rappel, Wouter-Jan
通讯作者：
Rappel, Wouter-Jan
影响因子：
64.5
作者：
Muzzey D;Gómez-Uribe CA;Mettetal JT;van Oudenaarden A
通讯作者：
van Oudenaarden A
影响因子：
11.8
作者：
Charest, Pascale G.;Shen, Zhouxin;Lakoduk, Ashley;Sasaki, Atsuo T.;Briggs, Steven P.;Firtel, Richard A.
通讯作者：
Firtel, Richard A.
影响因子：
3.4
作者：
Behar, Marcelo;Hao, Nan;Elston, Timothy C.
通讯作者：
Elston, Timothy C.