Arnold Sommerfeld Center for Theoretical Physics (ASC) and Center for NanoScience (CeNS), Department of Physics, Ludwig-Maximilians-Universität München, München, Germany.
Max Planck Institute of Biochemistry, Cellular Dynamics and Cell Patterning, Martinsried, Germany.
PLoS Comput Biol. 2013;9(12):e1003396. doi: 10.1371/journal.pcbi.1003396. Epub 2013 Dec 12.
Cell polarization is a prerequisite for essential processes such as cell migration, proliferation or differentiation. The yeast Saccharomyces cerevisiae under control of the GTPase Cdc42 is able to polarize without the help of cytoskeletal structures and spatial cues through a pathway depending on its guanine nucleotide dissociation inhibitor (GDI) Rdi1. To develop a fundamental understanding of yeast polarization we establish a detailed mechanistic model of GDI-mediated polarization. We show that GDI-mediated polarization provides precise spatial and temporal control of Cdc42 signaling and give experimental evidence for our findings. Cell cycle induced changes of Cdc42 regulation enhance positive feedback loops of active Cdc42 production, and thereby allow simultaneous switch-like regulation of focused polarity and Cdc42 activation. This regulation drives the direct formation of a unique polarity cluster with characteristic narrowing dynamics, as opposed to the previously proposed competition between transient clusters. As the key components of the studied system are conserved among eukaryotes, we expect our findings also to apply to cell polarization in other organisms.
细胞极化是细胞迁移、增殖或分化等基本过程的前提。在 GTPase Cdc42 的控制下，酵母 Saccharomyces cerevisiae 能够在没有细胞骨架结构和空间线索的帮助下通过依赖其鸟嘌呤核苷酸解离抑制剂 (GDI) Rdi1 的途径进行极化。为了深入了解酵母的极化，我们建立了一个详细的 GDI 介导的极化机制模型。我们表明，GDI 介导的极化提供了 Cdc42 信号的精确时空控制，并为我们的发现提供了实验证据。细胞周期诱导的 Cdc42 调节变化增强了活性 Cdc42 产生的正反馈环，从而允许同时进行集中极性和 Cdc42 激活的开关式调节。这种调节驱动了具有特征性变窄动力学的独特极性簇的直接形成，而不是以前提出的瞬态簇之间的竞争。由于所研究系统的关键组件在真核生物中是保守的，我们预计我们的发现也适用于其他生物体的细胞极化。
