CIP2A acts as a scaffold for CEP192-mediated microtubule organizing center assembly by recruiting Plk1 and aurora A during meiotic maturation

Development. 2017 Oct 15;144(20):3829-3839. doi: 10.1242/dev.158584. Epub 2017 Sep 21.

Abstract

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.

Keywords: Aurora kinase A; CEP192; CIP2A; Microtubule organizing center; Oocyte meiosis; Plk1.

MeSH terms

  • Animals
  • Antigens / metabolism
  • Aurora Kinase A / genetics*
  • Autoantigens / genetics
  • Autoantigens / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Centrosome / metabolism
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / physiology*
  • Chromosome Segregation
  • Cytoplasm / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Meiosis
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Microtubule-Organizing Center*
  • Microtubules / metabolism
  • Oocytes / metabolism
  • Ovary / metabolism
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • RNA, Small Interfering / metabolism
  • Spindle Apparatus / metabolism

Substances

  • Antigens
  • Autoantigens
  • CEP192 protein, mouse
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • KIAA1524 protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • pericentrin
  • Aurka protein, mouse
  • Aurora Kinase A
  • Protein Serine-Threonine Kinases