Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition
Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition
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DOI：
10.3390/cells9081769
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发表时间：
2020-08-01
期刊：
影响因子：
6
通讯作者：
Vavylonis, Dimitrios
中科院分区：
文献类型：
--
作者：
Khalili, Bita;Lovelace, Hailey D.;Vavylonis, Dimitrios
细胞通过调节膜结合小 GTP 酶在活性 GTP 结合和非活性 GDP 结合形式之间极化以生长、运动或交配。激活剂（GEF、GTP 交换因子）和抑制剂（GAP、GTP 酶激活蛋白）提供正反馈和负反馈。我们表明，曲面上的反应扩散模型解释了模型生物裂殖酵母极化的关键特征。该模型使用扩散系数和解离速率的测量值来实现 Cdc42 膜扩散，并假设有限的 GEF 池（蛋白质 Gef1 和 Scd1），如之前的芽殖酵母模型一样。该模型包括两种类型的GAP，一种代表尖端局部GAP，例如Rga3；另一种代表尖端局部GAP，例如Rga3。一种代表侧局域间隙，例如 Rga4 和 Rga6，我们假设它们在快速和慢速扩散状态之间切换。调整未知的速率常数后，该模型再现了细胞尖端的活性 Cdc42 区域以及细胞尖端和侧面的 GEF 和 GAP 定位模式。该模型再现了观察到的尖端到尖端的振荡，周期为几分钟，以及不对称到对称的振荡转变（对应于 NETO“新端起飞”），假设 GEF 的限制量随着细胞尺寸的增加而增加。
Cells polarize for growth, motion, or mating through regulation of membrane-bound small GTPases between active GTP-bound and inactive GDP-bound forms. Activators (GEFs, GTP exchange factors) and inhibitors (GAPs, GTPase activating proteins) provide positive and negative feedbacks. We show that a reaction-diffusion model on a curved surface accounts for key features of polarization of model organism fission yeast. The model implements Cdc42 membrane diffusion using measured values for diffusion coefficients and dissociation rates and assumes a limiting GEF pool (proteins Gef1 and Scd1), as in prior models for budding yeast. The model includes two types of GAPs, one representing tip-localized GAPs, such as Rga3; and one representing side-localized GAPs, such as Rga4 and Rga6, that we assume switch between fast and slow diffusing states. After adjustment of unknown rate constants, the model reproduces active Cdc42 zones at cell tips and the pattern of GEF and GAP localization at cell tips and sides. The model reproduces observed tip-to-tip oscillations with periods of the order of several minutes, as well as asymmetric to symmetric oscillations transitions (corresponding to NETO "new end take off"), assuming the limiting GEF amount increases with cell size.