Wang HaiYang, Choe Min Ho, Lee In-Won, Namgoong Suk, Kim Jae-Sung, Kim Nam-Hyung, Oh Jeong Su
Department of Animal Sciences, Chungbuk National University, Cheongju 28644, Korea.
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.
Development. 2017 Oct 15;144(20):3829-3839. doi: 10.1242/dev.158584. Epub 2017 Sep 21.
In somatic cells spindle microtubules are nucleated from centrosomes that act as major microtubule organizing centers (MTOCs), whereas oocytes form meiotic spindles by assembling multiple acentriolar MTOCs without canonical centrosomes. Aurora A and Plk1 are required for these events, but the underlying mechanisms remain largely unknown. Here we show that CIP2A regulates MTOC organization by recruiting aurora A and Plk1 at spindle poles during meiotic maturation. CIP2A colocalized with pericentrin at spindle poles with a few distinct cytoplasmic foci. Although CIP2A has been identified as an endogenous inhibitor of protein phosphatase 2A (PP2A), overexpression of CIP2A had no effect on meiotic maturation. Depletion of CIP2A perturbed normal spindle organization and chromosome alignment by impairing MTOC organization. Importantly, CIP2A was reciprocally associated with CEP192, promoting recruitment of aurora A and Plk1 at MTOCs. CIP2A was phosphorylated by Plk1 at S904, which targets CIP2A to MTOCs and facilitates MTOC organization with CEP192. Our results suggest that CIP2A acts as a scaffold for CEP192-mediated MTOC assembly by recruiting Plk1 and aurora A during meiotic maturation in mouse oocytes.
在体细胞中，纺锤体微管由作为主要微管组织中心（MTOC）的中心体产生，而卵母细胞通过组装多个无典型中心体的无中心粒MTOC形成减数分裂纺锤体。Aurora A和Plk1是这些过程所必需的，但潜在机制仍 largely未知。在这里，我们表明CIP2A在减数分裂成熟过程中通过在纺锤体极招募Aurora A和Plk1来调节MTOC组织。CIP2A与中心粒外周蛋白在纺锤体极共定位，并有一些不同的细胞质焦点。虽然CIP2A已被鉴定为蛋白磷酸酶2A（PP2A）的内源性抑制剂，但CIP2A的过表达对减数分裂成熟没有影响。CIP2A的缺失通过损害MTOC组织扰乱了正常的纺锤体组织和染色体排列。重要的是，CIP2A与CEP192相互关联，促进Aurora A和Plk1在MTOC处的招募。CIP2A在S904处被Plk1磷酸化，这将CIP2A靶向MTOC，并促进与CEP192的MTOC组织。我们的结果表明，CIP2A在小鼠卵母细胞减数分裂成熟过程中通过招募Plk1和Aurora A作为CEP192介导的MTOC组装的支架。
