Wu Chi-Fang, Chiou Jian-Geng, Minakova Maria, Woods Benjamin, Tsygankov Denis, Zyla Trevin R, Savage Natasha S, Elston Timothy C, Lew Daniel J
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, United States.
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Elife. 2015 Nov 2;4:e11611. doi: 10.7554/eLife.11611.
Polarity establishment in many cells is thought to occur via positive feedback that reinforces even tiny asymmetries in polarity protein distribution. Cdc42 and related GTPases are activated and accumulate in a patch of the cortex that defines the front of the cell. Positive feedback enables spontaneous polarization triggered by stochastic fluctuations, but as such fluctuations can occur at multiple locations, how do cells ensure that they make only one front? In polarizing cells of the model yeast Saccharomyces cerevisiae, positive feedback can trigger growth of several Cdc42 clusters at the same time, but this multi-cluster stage rapidly evolves to a single-cluster state, which then promotes bud emergence. By manipulating polarity protein dynamics, we show that resolution of multi-cluster intermediates occurs through a greedy competition between clusters to recruit and retain polarity proteins from a shared intracellular pool.
许多细胞中的极性建立被认为是通过正反馈来实现的，这种正反馈会强化极性蛋白分布中即使是微小的不对称性。Cdc42及相关的GTP酶被激活并聚集在界定细胞前端的皮质区域。正反馈使得由随机波动引发的自发极化成为可能，但由于这种波动可能在多个位置发生，细胞如何确保它们只形成一个前端呢？在模式酵母酿酒酵母的极化细胞中，正反馈可同时触发多个Cdc42簇的生长，但这个多簇阶段会迅速演变为单簇状态，进而促进芽的出现。通过操纵极性蛋白的动态变化，我们发现多簇中间体的解析是通过簇之间的贪婪竞争来实现的，以从共享的细胞内池中招募和保留极性蛋白。
