The Clp1p/Flp1p phosphatase ensures completion of cytokinesis in response to minor perturbation of the cell division machinery in Schizosaccharomyces pombe
The Clp1p/Flp1p phosphatase ensures completion of cytokinesis in response to minor perturbation of the cell division machinery in Schizosaccharomyces pombe
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DOI：
10.1242/jcs.01244
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发表时间：
2004-08-01
影响因子：
4
通讯作者：
Balasubramanian, MK
中科院分区：
文献类型：
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作者：
Mishra, M;Karagiannis, J;Balasubramanian, MK
分裂酵母在肌动球蛋白环的形成和功能上有缺陷，在细胞质分裂失败后表现出延长的G2延迟。这种G2延迟取决于SIN（细胞质分裂所必需的信号网络）和非必需的Cdc14p家族磷酸酶Clp1p/Flp1p，该酶被认为表明细胞质分裂检查点机制。然而，这种提出的Clp1p/ flp1p依赖性检查点的生理相关性尚不清楚，因为所有先前的研究都是在完全受限的条件下使用基本肌动球蛋白环组分的突变进行的，因此无论检查点是否存在，这些细胞都会死亡。在这里，我们发现细胞质分裂的延迟是由细胞动力学机制的不同组成部分的轻微扰动引起的，通常只会引起轻微的缺陷，当Clp1p/Flp1p失活时就会致命。此外，我们发现Clp1p/Flp1p不仅能抑制核分裂的进一步进行，还能维持受损的肌动球蛋白环以促进细胞分裂的完成。SIN的异位激活明显绕过了Clp1p/Flp1p对G2延迟和完成细胞分裂的要求。我们得出的结论是，当细胞分裂装置受到轻微干扰时，Clp1p/ flp1p依赖性细胞动力学检查点提供了以前未被识别的细胞存活优势。
Fission yeast mutants defective in actomyosin ring formation and function exhibit a prolonged G2 delay following cytokinesis failure. This G2 delay depends on the SIN, a signaling network essential for cytokinesis, and the non-essential Cdc14p family phosphatase, Clp1p/Flp1p and has been proposed to signify a cytokinesis checkpoint mechanism. However, the physiological relevance of this proposed Clp1p/Flp1p-dependent checkpoint is unclear because all previous studies were carried out using mutations in essential actomyosin ring components under fully restrictive conditions and thus these cells would have died regardless of the presence of the checkpoint. Here we show that delays in cytokinesis caused by minor perturbations to different components of the cytokinetic machinery, which normally cause only mild defects, become lethal when Clp1p/Flp1p is inactivated. In addition, we show that Clp1p/Flp1p does not function simply to inhibit further rounds of nuclear division, but also allows damaged actomyosin rings to be maintained to facilitate completion of cell division. Ectopic activation of the SIN significantly bypasses the requirement of Clp1p/Flp1p for G2 delay as well as for completion of cytokinesis. We conclude that the Clp1p/Flp1p-dependent cytokinesis checkpoint provides a previously unrecognized cell survival advantage when the cell division apparatus is mildly perturbed.