Polarization of diploid daughter cells directed by spatial cues and GTP hydrolysis of Cdc42 budding yeast.
Polarization of diploid daughter cells directed by spatial cues and GTP hydrolysis of Cdc42 budding yeast.
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DOI：
10.1371/journal.pone.0056665
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Park HO
中科院分区：
文献类型：
--
作者：
Lo WC;Lee ME;Narayan M;Chou CS;Park HO
细胞极化发生在通常由空间线索决定的单一轴上。发芽酵母的细胞表现出一种特征的发芽模式，这取决于细胞类型的特定皮质标记，反映了细胞极化位置的遗传编程。在不同类型的细胞中，CDC42GTP酶在细胞极化过程中起着关键作用。尽管以前对发芽酵母的研究表明，正反馈环使CDC42变得极化，但这些机制不包括空间线索，忽略了发芽的正常模式。在这里，我们结合活细胞成像和数学模型来理解二倍体子代细胞如何优先在前一个分裂部位远端的极点建立极性。活细胞成像显示，二倍体的子代细胞表现出动态极化，定位于芽尖直到M期，在胞质分裂时定位到分裂部位，然后定位到下一个G1期的远端。子细胞对远端萌发的强烈偏向需要远端极标签Bud8和Rga1，这是一种CDC42的GTP酶激活蛋白，它抑制细胞质分裂部位的萌发。出乎意料的是，我们还发现，超过50%的缺乏Rga1的子细胞在芽尖和远端表现出持续的Cdc42-GTP极化，这揭示了Rga1在Cdc42的时空调节中的额外作用，从而在极化生长模式中。数学模型确实揭示了在二倍体子代细胞的远端有强大的CDC42-GTP聚集，尽管具有里程碑意义的线索有随机扰动。此外，当模型中添加的噪声扰动了分割点的标志性能级和初始能级时，模型预测了不同的Cdc42-GTP极化动力学。
Cell polarization occurs along a single axis that is generally determined by a spatial cue. Cells of the budding yeast exhibit a characteristic pattern of budding, which depends on cell-type-specific cortical markers, reflecting a genetic programming for the site of cell polarization. The Cdc42 GTPase plays a key role in cell polarization in various cell types. Although previous studies in budding yeast suggested positive feedback loops whereby Cdc42 becomes polarized, these mechanisms do not include spatial cues, neglecting the normal patterns of budding. Here we combine live-cell imaging and mathematical modeling to understand how diploid daughter cells establish polarity preferentially at the pole distal to the previous division site. Live-cell imaging shows that daughter cells of diploids exhibit dynamic polarization of Cdc42-GTP, which localizes to the bud tip until the M phase, to the division site at cytokinesis, and then to the distal pole in the next G1 phase. The strong bias toward distal budding of daughter cells requires the distal-pole tag Bud8 and Rga1, a GTPase activating protein for Cdc42, which inhibits budding at the cytokinesis site. Unexpectedly, we also find that over 50% of daughter cells lacking Rga1 exhibit persistent Cdc42-GTP polarization at the bud tip and the distal pole, revealing an additional role of Rga1 in spatiotemporal regulation of Cdc42 and thus in the pattern of polarized growth. Mathematical modeling indeed reveals robust Cdc42-GTP clustering at the distal pole in diploid daughter cells despite random perturbation of the landmark cues. Moreover, modeling predicts different dynamics of Cdc42-GTP polarization when the landmark level and the initial level of Cdc42-GTP at the division site are perturbed by noise added in the model.
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影响因子：
64.5
作者：
CHANT, J;HERSKOWITZ, I
通讯作者：
HERSKOWITZ, I
影响因子：
56.9
作者：
Chen, T;Hiroko, T;Fujita, A
通讯作者：
Fujita, A
影响因子：
3.2
作者：
FREIFELDER, D
通讯作者：
FREIFELDER, D
影响因子：
3.5
作者：
Fujita, A;Lord, M;Chant, J
通讯作者：
Chant, J
影响因子：
3.3
作者：
Kang, PJ;Angerman, E;Park, HO
通讯作者：
Park, HO