Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA.
Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Curr Biol. 2020 Feb 24;30(4):715-722.e3. doi: 10.1016/j.cub.2019.12.027. Epub 2020 Jan 30.
Polo-like kinases (PLKs) have numerous roles in both mitosis and meiosis, including functions related to chromosome segregation, cohesin removal, and kinetochore orientation [1-7]. PLKs require specific regulation during meiosis to control those processes. Genetic studies demonstrate that the Drosophila PLK Polo kinase (Polo) is inhibited by the female meiosis-specific protein Matrimony (Mtrm) in a stoichiometric manner [8]. Drosophila Polo localizes strongly to kinetochores and to central spindle microtubules during prometaphase and metaphase I of female meiosis [9, 10]. Mtrm protein levels increase dramatically after nuclear envelope breakdown [11]. We show that Mtrm is enriched along the meiotic spindle and that loss of mtrm results in mislocalization of the catalytically active form of Polo. The mtrm gene is haploinsufficient, and heterozygosity for mtrm (mtrm/) results in high levels of achiasmate chromosome missegregation [8, 12]. In mtrm/ heterozygotes, there is a low level of sister centromere separation, as well as precocious loss of cohesion along the arms of achiasmate chromosomes. However, mtrm-null females are sterile [13], and sister chromatid cohesion is abolished on all chromosomes, leading to a failure to properly congress or orient chromosomes in metaphase I. These data demonstrate a requirement for the inhibition of Polo, perhaps by sequestering Polo to the microtubules during Drosophila melanogaster female meiosis and suggest that catalytically active Polo is a distinct subset of the total Polo population within the oocyte that requires its own regulation.
丝氨酸/苏氨酸激酶（PLKs）在有丝分裂和减数分裂中都具有多种功能，包括与染色体分离、黏连蛋白去除和动粒定向相关的功能[1-7]。PLKs 在减数分裂中需要特定的调节来控制这些过程。遗传研究表明，果蝇 PLK 丝氨酸/苏氨酸激酶（Polo）以化学计量的方式被减数分裂特异性蛋白 Matrimony（Mtrm）抑制[8]。果蝇 Polo 在有丝分裂前期和减数分裂 I 中期强烈定位于动粒和中心纺锤体微管[9,10]。Mtrm 蛋白水平在核膜破裂后急剧增加[11]。我们发现 Mtrm 沿减数分裂纺锤体富集，并且 mtrm 缺失导致催化活性形式的 Polo 定位错误。mtrm 基因是单倍不足的，mtrm 杂合子（mtrm/）导致非同源染色体错误分离的水平很高[8,12]。在 mtrm/杂合子中，姐妹着丝粒分离程度低，以及非同源染色体臂上的黏连蛋白过早丢失。然而，mtrm 缺失的雌性是不育的[13]，所有染色体上的姐妹染色单体黏合都被废除，导致在减数分裂 I 中期染色体不能正确会聚或定向。这些数据表明 Polo 的抑制是必需的，可能是通过将 Polo 隔离到微管中来实现的，这在果蝇黑素体雌性减数分裂中是如此，并表明催化活性 Polo 是卵母细胞中总 Polo 群体的一个独特子集，需要自身的调节。
