Ste12/Fab1 phosphatidylinositol-3-phosphate 5-kinase is required for nitrogen-regulated mitotic commitment and cell size control.
Ste12/Fab1 phosphatidylinositol-3-phosphate 5-kinase is required for nitrogen-regulated mitotic commitment and cell size control.
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DOI：
10.1371/journal.pone.0172740
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Petersen J
中科院分区：
文献类型：
--
作者：
Cobley D;Hálová L;Schauries M;Kaczmarek A;Franz-Wachtel M;Du W;Krug K;Maček B;Petersen J
细胞生长和细胞周期进程的紧密耦合使细胞能够调整其分裂速度，从而调整其大小，以适应不同营养环境中的增殖需求。营养胁迫促进雷帕霉素复合体靶标1(TORC1)活性的抑制。在分裂酵母中，TORC1活性降低会提前有丝分裂的开始，并在细胞尺寸缩小的情况下将生长切换到持续的增殖。对在氮胁迫下未能促进有丝分裂的突变体进行筛选，在PIKfyve 1-磷脂酰肌醇-3-磷酸5-激酶裂解酵母同系物STE12中发现了一个突变体。Ste12PIKFYVE缺失突变体在氮素降低到较差的氮素(脯氨酸)生长条件后，不能提前细胞周期来缩小细胞尺寸。虽然已经确定PI(3，5)P2信号是自噬所必需的，并且Ste12PIKFYVE突变体具有增大的空泡(酵母溶酶体)，但阻止自噬或独立增大空泡的突变体对氮控制有丝分裂承诺都没有任何影响。在Ste12PIKFYVE缺失突变体中加入雷帕霉素可以减小分裂时的细胞大小，这表明Ste12PIKFYVE可能在TORC1的上游起作用。STE12突变体对Torin1(TOR抑制剂)的敏感性增加。然而，在STE12缺失突变体中没有观察到对TORC1或TORC2活性的重大影响。综上所述，Ste12PIKFYVE是氮胁迫促进有丝分裂以减小分裂时细胞大小所必需的。
Tight coupling of cell growth and cell cycle progression enable cells to adjust their rate of division, and therefore size, to the demands of proliferation in varying nutritional environments. Nutrient stress promotes inhibition of Target Of Rapamycin Complex 1 (TORC1) activity. In fission yeast, reduced TORC1 activity advances mitotic onset and switches growth to a sustained proliferation at reduced cell size. A screen for mutants, that failed to advance mitosis upon nitrogen stress, identified a mutant in the PIKFYVE 1-phosphatidylinositol-3-phosphate 5-kinase fission yeast homolog Ste12. Ste12PIKFYVE deficient mutants were unable to advance the cell cycle to reduce cell size after a nitrogen downshift to poor nitrogen (proline) growth conditions. While it is well established that PI(3,5)P2 signalling is required for autophagy and that Ste12PIKFYVE mutants have enlarged vacuoles (yeast lysosomes), neither a block to autophagy or mutants that independently have enlarged vacuoles had any impact upon nitrogen control of mitotic commitment. The addition of rapamycin to Ste12PIKFYVE deficient mutants reduced cell size at division to suggest that Ste12PIKFYVE possibly functions upstream of TORC1. ste12 mutants display increased Torin1 (TOR inhibitor) sensitivity. However, no major impact on TORC1 or TORC2 activity was observed in the ste12 deficient mutants. In summary, Ste12PIKFYVE is required for nitrogen-stress mediated advancement of mitosis to reduce cell size at division.