title: Microtubules stabilize cell polarity by localizing rear signals.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219.
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Guo
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15219 yuliwang@andrew.cmu.edu.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Wang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001683:Biological Clocks; D015415:Biomarkers; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity; D003198:Computer Simulation; D004847:Epithelial Cells / Q000502:physiology / Q000648:ultrastructure; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008868:Microtubule Proteins / Q000032:analysis; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D008954:Models, Biological; D055213:Retinal Pigment Epithelium / Q000166:cytology; D060589:Zyxin / Q000032:analysis
chemical_list: D015415:Biomarkers; D008868:Microtubule Proteins; C092842:ZYX protein, human; C498285:Zyx protein, mouse; D060589:Zyxin
keywords: LEGI; cell migration; cell polarity; focal adhesion; microtubules