Principles that govern competition or co-existence in Rho-GTPase driven polarization
Principles that govern competition or co-existence in Rho-GTPase driven polarization
复制标题
DOI：
10.1371/journal.pcbi.1006095
复制
发表时间：
2018-04-01
影响因子：
4.3
通讯作者：
Lew, Daniel J.
中科院分区：
文献类型：
--
作者：
Chiou, Jian-Geng;Ramirez, Samuel A.;Lew, Daniel J.
Rho-GTP酶是极性建立和细胞形态的主要调节剂。正反馈使得Rho-GTP酶能够在细胞皮层集中成簇，从那里它们调节细胞骨架。不同的细胞类型可重复地产生一个（例如迁移细胞的前部）或几个簇（例如神经元的多个树突），但单极或多极结果的机制基础尚不清楚。Rho-GTdR电路的设计原则是基于Rho-GTdR生物化学保守方面的双组分反应扩散模型。一些这样的模型显示集群之间的快速赢家通吃竞争，产生单极结果。其他模型允许集群长期共存。我们研究了一类简单的模型的行为，并表明，虽然竞争的时间尺度变化很大，这取决于模型参数，一个单一的因素解释了这种变化的大部分。的主导因素涉及的程度，在集群中的最大活性GTdR浓度接近“饱和点”由模型参数确定。我们认为，饱和度和饱和度对竞争的影响反映了Rho-GTdR极性机制的基本特性，而不管具体的反馈机制如何，它预测系统是否会产生单极或多极结果。
Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a "saturation point" determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism, which predict whether the system will generate unipolar or multipolar outcomes.