細(xì)胞極化對于正常的細(xì)胞分化和運動有著重要意義,。保守的鳥嘌呤核苷三磷酸酶（GTPase）Cdc42通過調(diào)節(jié)細(xì)胞骨架的不對稱性建立極化狀態(tài),。但是，其具體機制仍很不清楚,。Science雜志5月17日在線發(fā)表了Maitreyi Das等人的研究報告“Oscillatory Dynamics of Cdc42 GTPase in the Control of Polarized Growth”,。進一步揭示了其中的細(xì)節(jié)。
以往研究表明,，細(xì)胞通過活化細(xì)胞膜表面的Rho家族蛋白Cdc42來促進極化生長,。研究者結(jié)合實驗和計算模擬手段研究裂殖酵母細(xì)胞的二極化生長起始過程。他們首先利用熒光標(biāo)記物分別標(biāo)記活化型Cdc42,、Cdc42,、 Cdc42的活化因子Scd1以及支架蛋白Scd2，然后檢測這些分子在細(xì)胞表面的信號強度,。結(jié)果發(fā)現(xiàn),，在極化細(xì)胞的頂端，這些熒光信號的強度呈現(xiàn)出負(fù)相關(guān)的波動,，其振蕩周期平均為5分鐘,。這一現(xiàn)象提示，在活化Cdc42或其調(diào)控因子之間存在著競爭關(guān)系,，而且具有正反饋或延遲的負(fù)反饋,。Cdc42振蕩和空間分布對Cdc42活化因子Gef1的數(shù)量和Cdc42依賴性激酶Pak1的活性敏感。
目前看來,，調(diào)控Cdc42振蕩和空間自我組織的反饋機制,，是裂殖酵母細(xì)胞感知極化狀態(tài)，和調(diào)控自身形態(tài)的靈活機制,。（生物谷Bioon.com）
doi:10.1126/science.1218377
PMC:
PMID:
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.
