Cell polarization is of paramount importance for proliferation, differentiation, development, and it is altered during carcinogenesis. Polarization is a reversible process controlled by positive and negative feedback loops. How polarized factors are redistributed is not fully understood and is the focus of this work. In Saccharomyces cerevisiae, mutants defective in haspin kinase exhibit stably polarized landmarks and are sensitive to mitotic delays. Here, we report a new critical role for haspin in polarisome dispersion; failure to redistribute polarity factors, in turn, leads to nuclear segregation defects and cell lethality. We identified a mitotic role for GTP-Ras in regulating the local activation of the Cdc42 GTPase, resulting in its dispersal from the bud tip to a homogeneous distribution over the plasma membrane. GTP-Ras2 physically interacts with Cdc24 regulateing its mitotic distribution. Haspin is shown to promote a mitotic shift from a bud tip-favored to a homogenous PM fusion of Ras-containing vesicles. In absence of haspin, active Ras is not redistributed from the bud tip; Cdc24 remains hyperpolarized promoting the activity of Cdc42 at the bud tip, and the polarisome fails to disperse leading to erroneously positioned mitotic spindle, defective nuclear segregation, and cell death after mitotic delays. These findings describe new functions for key factors that modulate cell polarization and mitotic events, critical processes involved in development and tumorigenesis.

细胞极化对于增殖、分化、发育至关重要，并且在癌发生过程中会发生改变。极化是一个由正反馈回路和负反馈回路控制的可逆过程。极化因素如何重新分配尚不完全清楚，这是这项工作的重点。在酿酒酵母中，haspin激酶缺陷的突变体表现出稳定的极化标志并且对有丝分裂延迟敏感。在这里，我们报告了 haspin 在极化体色散中的新关键作用；极性因子无法重新分配反过来会导致核分离缺陷和细胞致死。我们确定了 GTP-Ras 在调节 Cdc42 GTPase 局部激活中的有丝分裂作用，导致其从芽尖分散到质膜上均匀分布。GTP-Ras2 与 Cdc24 发生物理相互作用，调节其有丝分裂分布。Haspin 可促进有丝分裂从芽尖偏好转变为含有 Ras 的囊泡的同质 PM 融合。在缺乏搭扣的情况下，活性 Ras 不会从芽尖重新分布；Cdc24 保持超极化，促进芽尖处 Cdc42 的活性，并且极化体无法分散，导致有丝分裂纺锤体错误定位、核分离缺陷以及有丝分裂延迟后细胞死亡。这些发现描述了调节细胞极化和有丝分裂事件、参与发育和肿瘤发生的关键过程的关键因子的新功能。