Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, Italy.
PLoS Genet. 2012;8(4):e1002670. doi: 10.1371/journal.pgen.1002670. Epub 2012 Apr 26.
The first step towards cytokinesis in budding yeast is the assembly of a septin ring at the future site of bud emergence. Integrity of this ring is crucial for cytokinesis, proper spindle positioning, and the spindle position checkpoint (SPOC). This checkpoint delays mitotic exit and cytokinesis as long as the anaphase spindle does not properly align with the division axis. SPOC signalling requires the Kin4 protein kinase and the Kin4-regulating Elm1 kinase, which also controls septin dynamics. Here, we show that the two redundant ubiquitin-ligases Dma1 and Dma2 control septin dynamics and the SPOC by promoting the efficient recruitment of Elm1 to the bud neck. Indeed, dma1 dma2 mutant cells show reduced levels of Elm1 at the bud neck and Elm1-dependent activation of Kin4. Artificial recruitment of Elm1 to the bud neck of the same cells is sufficient to re-establish a normal septin ring, proper spindle positioning, and a proficient SPOC response in dma1 dma2 cells. Altogether, our data indicate that septin dynamics and SPOC function are intimately linked and support the idea that integrity of the bud neck is crucial for SPOC signalling.
在出芽酵母中,细胞分裂的第一步是在芽出现的未来位置组装一个隔膜环。这个环的完整性对于细胞分裂、纺锤体的正确定位和纺锤体位置检查点(SPOC)至关重要。只要后期纺锤体没有正确地与分裂轴对齐,SPOC 检查点就会延迟有丝分裂的退出和细胞分裂。SPOC 信号需要 Kin4 蛋白激酶和调节 Kin4 的 Elm1 激酶,它们也控制着隔膜的动力学。在这里,我们表明,两个冗余的泛素连接酶 Dma1 和 Dma2 通过促进 Elm1 向芽颈的有效募集来控制隔膜的动力学和 SPOC。事实上,dma1 dma2 突变体细胞在芽颈处的 Elm1 水平降低,并且依赖于 Elm1 的 Kin4 激活减少。将 Elm1 人工募集到相同细胞的芽颈中足以在 dma1 dma2 细胞中重新建立正常的隔膜环、正确的纺锤体定位和有效的 SPOC 反应。总的来说,我们的数据表明,隔膜动力学和 SPOC 功能密切相关,并支持芽颈的完整性对于 SPOC 信号至关重要的观点。