Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Sci Signal. 2010 Dec 14;3(152):ra89. doi: 10.1126/scisignal.2001056.
Cell chemotaxis has been characterized as the formation of a front-back axis that is triggered by a gradient of chemoattractant; however, chemotaxis is accompanied by more complicated behaviors. These include migration in a straight line with a stable axis [the stable single-axis (SSA) pattern] and repeated splitting of the leading edge of the cell into two regions, followed by the "choice" of one of these as the new leading edge [the split and choice (S&C) pattern]. Indeed, transition between these two behaviors can be observed in individual cells. However, the conceptual framework of the network of signaling molecules that generates these patterns remains to be clarified. We confirmed theoretically that a system that has positive and negative feedback loops involving the reciprocal cycling between the membrane and the cytosol of molecules that promote membrane protrusion or retraction generates SSA and S&C patterns of migratory behavior under similar conditions. We also predicted properties of the instabilities of such a system, which are essential for the generation of these behaviors, and we verified their existence in chemotaxing cells. Our research provides a simple model of network structure for chemotactic behaviors, including cell polarization.
细胞趋化性的特征是形成前后轴，该轴由趋化剂梯度触发；然而，趋化性伴随着更复杂的行为。这些行为包括以稳定的轴呈直线迁移（稳定单轴模式）和细胞前缘反复分裂成两个区域，然后“选择”其中一个作为新的前缘（分裂和选择模式）。事实上，在单个细胞中可以观察到这两种行为之间的转换。然而，产生这些模式的信号分子网络的概念框架仍有待阐明。我们从理论上证实，在类似条件下，一个包含正反馈和负反馈回路的系统，该系统涉及促进膜突出或缩回的分子在膜和细胞质之间的循环，会产生 SSA 和 S&C 迁移行为模式。我们还预测了该系统不稳定性的特性，这些特性对于产生这些行为是必不可少的，并在趋化性细胞中验证了它们的存在。我们的研究为包括细胞极化在内的趋化行为提供了一个简单的网络结构模型。
