Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, United States.
Elife. 2021 Apr 26;10:e58768. doi: 10.7554/eLife.58768.
The diversity of cell morphologies arises, in part, through regulation of cell polarity by Rho-family GTPases. A poorly understood but fundamental question concerns the regulatory mechanisms by which different cells generate different numbers of polarity sites. Mass-conserved activator-substrate (MCAS) models that describe polarity circuits develop multiple initial polarity sites, but then those sites engage in competition, leaving a single winner. Theoretical analyses predicted that competition would slow dramatically as GTPase concentrations at different polarity sites increase toward a 'saturation point', allowing polarity sites to coexist. Here, we test this prediction using budding yeast cells, and confirm that increasing the amount of key polarity proteins results in multiple polarity sites and simultaneous budding. Further, we elucidate a novel design principle whereby cells can switch from competition to equalization among polarity sites. These findings provide insight into how cells with diverse morphologies may determine the number of polarity sites.
细胞形态的多样性部分源于 Rho 家族 GTPases 对细胞极性的调控。一个尚未被充分理解但非常基本的问题是,不同的细胞如何通过调节机制产生不同数量的极性位点。描述极性回路的质量守恒激活物-基质(MCAS)模型会产生多个初始极性位点,但随后这些位点会相互竞争,最终只剩下一个胜者。理论分析预测,随着不同极性位点的 GTPase 浓度朝着“饱和点”增加,竞争会显著减缓,从而允许极性位点共存。在这里,我们使用出芽酵母细胞来检验这一预测,并证实增加关键极性蛋白的数量会导致多个极性位点和同时出芽。此外,我们还阐明了一种新的设计原则,即细胞可以在极性位点之间从竞争切换到均衡。这些发现为具有不同形态的细胞如何确定极性位点的数量提供了深入的了解。