Nguyen Alexandra L, Gentilello Amanda S, Balboula Ahmed Z, Shrivastava Vibha, Ohring Jacob, Schindler Karen
Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
J Cell Sci. 2014 Dec 1;127(Pt 23):5066-78. doi: 10.1242/jcs.158840. Epub 2014 Oct 14.
Meiosis I (MI), the division that generates haploids, is prone to errors that lead to aneuploidy in females. Haspin is a kinase that phosphorylates histone H3 on threonine 3, thereby recruiting Aurora kinase B (AURKB) and the chromosomal passenger complex (CPC) to kinetochores to regulate mitosis. Haspin and AURKC, an AURKB homolog, are enriched in germ cells, yet their significance in regulating MI is not fully understood. Using inhibitors and overexpression approaches, we show a role for haspin during MI in mouse oocytes. Haspin-perturbed oocytes display abnormalities in chromosome morphology and alignment, improper kinetochore-microtubule attachments at metaphase I and aneuploidy at metaphase II. Unlike in mitosis, kinetochore localization remained intact, whereas the distribution of the CPC along chromosomes was absent. The meiotic defects following haspin inhibition were similar to those observed in oocytes where AURKC was inhibited, suggesting that the correction of microtubule attachments during MI requires AURKC along chromosome arms rather than at kinetochores. Our data implicate haspin as a regulator of the CPC and chromosome segregation during MI, while highlighting important differences in how chromosome segregation is regulated between MI and mitosis.
减数分裂I（MI）是产生单倍体的分裂过程，在雌性中容易出现导致非整倍体的错误。Haspin是一种激酶，可将组蛋白H3的苏氨酸3磷酸化，从而将极光激酶B（AURKB）和染色体乘客复合体（CPC）募集到动粒上以调节有丝分裂。Haspin和AURKB的同源物AURKC在生殖细胞中富集，但其在调节MI中的意义尚未完全了解。使用抑制剂和过表达方法，我们展示了Haspin在小鼠卵母细胞MI过程中的作用。受Haspin干扰的卵母细胞在染色体形态和排列上显示异常，在中期I时动粒-微管附着不当，在中期II时出现非整倍体。与有丝分裂不同，动粒定位保持完整，而CPC沿染色体的分布缺失。Haspin抑制后的减数分裂缺陷与在抑制AURKC的卵母细胞中观察到的缺陷相似，这表明MI期间微管附着的校正需要AURKC沿染色体臂而非在动粒处发挥作用。我们的数据表明Haspin是MI期间CPC和染色体分离的调节因子，同时突出了MI和有丝分裂之间染色体分离调节方式的重要差异。
