正反馈调节导致细胞膜上活性信号分子的空间聚集和快速扩散
Positive Feedback Regulation Results in Spatial Clustering and Fast Spreading of Active Signaling Molecules on a Cell Membrane
摘要:
正反馈调节在细胞信号网络中普遍存在,通常导致响应于分级刺激的二元结果。然而,这种反馈的作用,在集群中,并在空间传播的激活分子,最近才得到赞赏。我们专注于后者,使用一个简单的模型开发的Ras激活的背景下,竞争的负反馈和正反馈机制。我们发现,正反馈,在缓慢扩散的存在下,在质膜上的活化分子的集群,和快速的空间扩散作为集群的前端传播以恒定的速度(取决于反馈强度)。团簇的活化物种的前进前沿是粗糙的,与缩放一致的Kardar-Parisi-Zhang(KPZ)方程在一维。我们的极小模型是一般的,足以描述在各种各样的生物网络中,在膜近端区域的活动受到反馈调节的信号转导。
英文摘要:
Positive feedback regulation is ubiquitous in cell signaling networks, often leading to binary outcomes in response to graded stimuli. However, the role of such feedbacks in clustering, and in spatial spreading of activated molecules, has come to be appreciated only recently. We focus on the latter, using a simple model developed in the context of Ras activation with competing negative and positive feedback mechanisms. We find that positive feedback, in the presence of slow diffusion, results in clustering of activated molecules on the plasma membrane, and rapid spatial spreading as the front of the cluster propagates with a constant velocity (dependent on the feedback strength). The advancing fronts of the clusters of the activated species are rough, with scaling consistent with the Kardar-Parisi-Zhang (KPZ) equation in one dimension. Our minimal model is general enough to describe signal transduction in a wide variety of biological networks where activity in the membrane-proximal region is subject to feedback regulation.
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