CIP2A acts as a scaffold for CEP192-mediated MTOC assembly by recruiting Plk1 and Aurora A during meiotic maturation

Abstract

In contrast to somatic cells where spindle microtubules are nucleated from centrosomes acting as major microtubule organizing centers (MTOCs), oocytes form meiotic spindles by assembling multiple acentriolar MTOCs without canonical centrosomes. Although Aurora A and Plk1 are required for these events, the underlying mechanisms remain largely unknown. Here we show that cancerous inhibitor of protein phosphatase 2A (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 specific 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 the recruitment of Aurora A and Plk1 at MTOCs. Moreover, CIP2A was phosphorylated by Plk1 at S904, which targets CIP2A to MTOCs and facilitates MTOC organization with CEP192. Collectively, 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.