细胞极化对于正常的细胞分化和运动有着重要意义。保守的鸟嘌呤核苷三磷酸酶（GTPase）Cdc42通过调节细胞骨架的不对称性建立极化状态。但是，其具体机制仍很不清楚。Science杂志5月17日在线发表了Maitreyi Das等人的研究报告“Oscillatory Dynamics of Cdc42 GTPase in the Control of Polarized Growth”。进一步揭示了其中的细节。
以往研究表明，细胞通过活化细胞膜表面的Rho家族蛋白Cdc42来促进极化生长。研究者结合实验和计算模拟手段研究裂殖酵母细胞的二极化生长起始过程。他们首先利用荧光标记物分别标记活化型Cdc42、Cdc42、 Cdc42的活化因子Scd1以及支架蛋白Scd2，然后检测这些分子在细胞表面的信号强度。结果发现，在极化细胞的顶端，这些荧光信号的强度呈现出负相关的波动，其振荡周期平均为5分钟。这一现象提示，在活化Cdc42或其调控因子之间存在着竞争关系，而且具有正反馈或延迟的负反馈。Cdc42振荡和空间分布对Cdc42活化因子Gef1的数量和Cdc42依赖性激酶Pak1的活性敏感。
目前看来，调控Cdc42振荡和空间自我组织的反馈机制，是裂殖酵母细胞感知极化状态，和调控自身形态的灵活机制。（生物谷Bioon.com）
doi:10.1126/science.1218377
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Oscillatory Dynamics of Cdc42 GTPase in the Control of Polarized Growth
Maitreyi Das1,*, Tyler Drake3,*, David J. Wiley1, Peter Buchwald1, Dimitrios Vavylonis3, Fulvia Verde
Cells promote polarized growth by activation of Rho-family protein Cdc42 at the cell membrane. We combined experiments and modeling to study bipolar growth initiation in fission yeast. Concentrations of a fluorescent marker for active Cdc42, Cdc42 protein, Cdc42-activator Scd1, and scaffold protein Scd2, exhibited anticorrelated fluctuations and oscillations with a 5-minute average period at polarized cell tips. These dynamics indicate competition for active Cdc42, or its regulators, and the presence of positive and delayed negative feedbacks. Cdc42 oscillations and spatial distribution were sensitive to the amounts of Cdc42-activator Gef1 and to the activity of Cdc42-dependent kinase Pak1, a negative regulator. Feedbacks regulating Cdc42 oscillations and spatial self-organization appear to provide a flexible mechanism for fission yeast cells to explore polarization states and control their morphology.
