Zhang Jian, Guo Wei-Hui, Wang Yu-Li
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219.
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219
Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16383-8. doi: 10.1073/pnas.1410533111. Epub 2014 Nov 3.
Microtubules are known to play an important role in cell polarity; however, the mechanism remains unclear. Using cells migrating persistently on micropatterned strips, we found that depolymerization of microtubules caused cells to change from persistent to oscillatory migration. Mathematical modeling in the context of a local-excitation-global-inhibition control mechanism indicated that this mechanism can account for microtubule-dependent oscillation, assuming that microtubules remove inhibitory signals from the front after a delayed generation. Experiments further supported model predictions that the period of oscillation positively correlates with cell length and that oscillation may be induced by inhibiting retrograde motors. We suggest that microtubules are required not for the generation but for the maintenance of cell polarity, by mediating the global distribution of inhibitory signals. Disassembly of microtubules induces cell oscillation by allowing inhibitory signals to accumulate at the front, which stops frontal protrusion and allows the polarity to reverse.
已知微管在细胞极性中发挥重要作用；然而，其机制仍不清楚。利用在微图案化条带上持续迁移的细胞，我们发现微管的解聚导致细胞从持续迁移转变为振荡迁移。在局部兴奋-全局抑制控制机制的背景下进行的数学建模表明，假设微管在延迟产生后从前部去除抑制信号，该机制可以解释微管依赖性振荡。实验进一步支持了模型预测，即振荡周期与细胞长度呈正相关，并且抑制逆行马达可能会诱导振荡。我们认为，微管不是产生细胞极性所必需的，而是通过介导抑制信号的全局分布来维持细胞极性。微管的拆卸通过允许抑制信号在前部积累来诱导细胞振荡，这会阻止前部突出并使极性反转。
