Directional sensing in eukaryotic chemotaxis: A balanced inactivation model
Directional sensing in eukaryotic chemotaxis: A balanced inactivation model
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DOI：
10.1073/pnas.0601302103
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发表时间：
2006-06-27
影响因子：
11.1
通讯作者：
Rappel, Wouter-Jan
中科院分区：
文献类型：
--
作者：
Levine, Herbert;Kessler, David A.;Rappel, Wouter-Jan
许多真核细胞，包括盘状网柄菌、成纤维细胞和中性粒细胞，能够以高灵敏度对化学引诱物梯度作出反应。最近的研究表明，在引入趋化梯度后，几种趋化途径组分表现出亚细胞重组，这不能被描述为外部梯度的简单放大。相反，这种重组具有开关的特征，导致明确的前后。在这里，我们提出了一种定向传感机制，其中两个第二信使以相等的速率产生。其中之一的扩散，再加上一个灭活方案，确保开关样的反应，外部梯度的梯度陡度和平均浓度的大范围。此外，我们的模型是能够扭转的亚细胞组织迅速，其响应多个同时的化学引诱剂来源是在最近的实验结果很好的协议。最后，我们提出，一个异源三聚体G蛋白的动力学可能允许我们的模型的一个特定的生化实现。
Many eukaryotic cells, including Dictyostefium discoideum amoebae, fibroblasts, and neutrophils, are able to respond to chemoattractant gradients with high sensitivity. Recent studies have demonstrated that, after the introduction of a chemoattractant gradient, several chemotaxis pathway components exhibit a subcellular reorganization that cannot be described as a simple amplification of the external gradient. Instead,this reorganization has the characteristics of a switch, leading to a well defined front and back. Here, we propose a directional sensing mechanism in which two second messengers are produced at equal rates. The diffusion of one of them, coupled with an inactivation scheme, ensures a switch-like response to external gradients for a large range of gradient steepness and average concentration. Furthermore, our model is able to reverse the subcellular organization rapidly, and its response to multiple simultaneous chemoattractant sources is in good agreement with recent experimental results. Finally, we propose that the dynamics of a heterotrimeric G protein might allow for a specific biochemical realization of our model.