Vardy Leah, Fujita Akiko, Toda Takashi
Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Genes Cells. 2002 Apr;7(4):365-73. doi: 10.1046/j.1365-2443.2002.00530.x.
The progression of cytokinesis requires cyclin B destruction by the anaphase promoting complex (APC/C) and, in fission yeast, activation of the septation initiation network (SIN) is also essential. The gamma-tubulin complex (gamma-TuC) localizes to the centrosome throughout the cell cycle and is directly involved in the organization of the mitotic spindle.
We have previously shown that the mutant defective in alp4+ (Spc97/GCP2) displays bipolar spindle defects due to a failure in the recruitment of the gamma-TuC on to the spindle pole body (SPB, the centrosome equivalent). Here we show that in these mutants the Mad2 checkpoint is activated, yet septation proceeds due to the untimely activation of the SIN. The Sid1 kinase, the downstream effector of the SIN, is recruited prematurely to both, instead of only one, of the SPBs, which triggers septation despite the presence of monopolar spindles. Remarkably, cyclin B levels, which would normally have declined, remain high at the SPB in septated mutant cells.
We propose a novel role of the gamma-TuC in inhibiting activation of the SIN until cyclin B is destroyed. Given the ubiquitous existence of the gamma-TuC, this mechanism may be conserved throughout evolution and function to couple cytokinesis to mitotic exit.
胞质分裂的进行需要后期促进复合物（APC/C）对细胞周期蛋白B的降解，并且在裂殖酵母中，隔膜起始网络（SIN）的激活也至关重要。γ-微管蛋白复合物（γ-TuC）在整个细胞周期中定位于中心体，并直接参与有丝分裂纺锤体的组织。
我们之前已经表明，由于alp4 +（Spc97 / GCP2）缺陷的突变体在将γ-TuC募集到纺锤体极体（SPB，相当于中心体）上失败，从而表现出双极纺锤体缺陷。在这里我们表明，在这些突变体中，Mad2检查点被激活，但由于SIN的过早激活，隔膜形成仍在继续。SIN的下游效应器Sid1激酶被过早募集到两个而不是仅一个SPB上，这导致尽管存在单极纺锤体但仍触发隔膜形成。值得注意的是，在已形成隔膜的突变体细胞中，通常会下降的细胞周期蛋白B水平在SPB处仍然很高。
我们提出γ-TuC在抑制SIN激活直到细胞周期蛋白B被降解方面具有新作用。鉴于γ-TuC普遍存在，这种机制可能在整个进化过程中保守，并起到将胞质分裂与有丝分裂退出相耦合的作用。
