A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization
A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization
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DOI：
10.1016/j.devcel.2005.08.014
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发表时间：
2005-10-01
影响因子：
11.8
通讯作者：
van Oudenaarden, A
中科院分区：
文献类型：
--
作者：
Ozbudak, EM;Becskei, A;van Oudenaarden, A
细胞极化通常是对不同的细胞外或细胞内线索的反应，例如营养梯度或皮质标志。然而，在没有这些线索的情况下，一些细胞仍然可以随机选择偏振轴。正反馈环促进GTdR Cdc42p的局部活化是芽殖酵母中该过程的核心。在这里，我们探讨自发极化过程中芽位点选择突变酵母细胞缺乏功能的地标。我们发现，这些细胞不选择一个单一的随机极化轴，但在细胞周期的G1期不断改变这个轴。这反映在随机探索细胞周边的激活Cdc42p的行波中。我们的综合计算和这些波的体内分析揭示了一个负反馈回路，与上述正反馈回路竞争，以调节Cdc42p活性，并赋予动态响应的强大启动细胞极化。
Cellular polarization is often a response to distinct extracellular or intracellular cues, such as nutrient gradients or cortical landmarks. However, in the absence of such cues, some cells can still select a polarization axis at random. Positive feedback loops promoting localized activation of the GTPase Cdc42p are central to this process in budding yeast. Here, we explore spontaneous polarization during bud site selection in mutant yeast cells that lack functional landmarks. We find that these cells do not select a single random polarization axis, but continuously change this axis during the G1 phase of the cell cycle. This is reflected in traveling waves of activated Cdc42p which randomly explore the cell periphery. Our integrated computational and in vivo analyses of these waves reveal a negative feedback loop that competes with the aforementioned positive feedback loops to regulate Cdc42p activity and confer dynamic responsiveness on the robust initiation of cell polarization.