McMillan J N, Sia R A, Lew D J
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Cell Biol. 1998 Sep 21;142(6):1487-99. doi: 10.1083/jcb.142.6.1487.
A morphogenesis checkpoint in budding yeast delays cell cycle progression in response to perturbations of cell polarity that prevent bud formation (Lew, D.J., and S.I. Reed. 1995. J. Cell Biol. 129:739- 749). The cell cycle delay depends upon the tyrosine kinase Swe1p, which phosphorylates and inhibits the cyclin-dependent kinase Cdc28p (Sia, R.A.L., H.A. Herald, and D.J. Lew. 1996. Mol. Biol. Cell. 7:1657- 1666). In this report, we have investigated the nature of the defect(s) that trigger this checkpoint. A Swe1p- dependent cell cycle delay was triggered by direct perturbations of the actin cytoskeleton, even when polarity establishment functions remained intact. Furthermore, actin perturbation could trigger the checkpoint even in cells that had already formed a bud, suggesting that the checkpoint directly monitors actin organization, rather than (or in addition to) polarity establishment or bud formation. In addition, we show that the checkpoint could detect actin perturbations through most of the cell cycle. However, the ability to respond to such perturbations by delaying cell cycle progression was restricted to a narrow window of the cell cycle, delimited by the periodic accumulation of the checkpoint effector, Swe1p.
芽殖酵母中的一个形态发生检查点会响应细胞极性的扰动而延迟细胞周期进程,这种扰动会阻止芽的形成(Lew,D.J.和S.I. Reed。1995年。《细胞生物学杂志》129:739 - 749)。细胞周期延迟依赖于酪氨酸激酶Swe1p,它会磷酸化并抑制细胞周期蛋白依赖性激酶Cdc28p(Sia,R.A.L.,H.A. Herald和D.J. Lew。1996年。《分子生物学细胞》7:1657 - 1666)。在本报告中,我们研究了触发此检查点的缺陷的性质。即使极性建立功能保持完整,肌动蛋白细胞骨架的直接扰动也会触发依赖Swe1p的细胞周期延迟。此外,肌动蛋白扰动甚至可以在已经形成芽的细胞中触发检查点,这表明该检查点直接监测肌动蛋白组织,而不是(或除了)极性建立或芽的形成。另外,我们表明该检查点在细胞周期的大部分时间都能检测到肌动蛋白扰动。然而,通过延迟细胞周期进程来响应此类扰动的能力仅限于细胞周期的一个狭窄窗口,该窗口由检查点效应物Swe1p的周期性积累界定。