Cullin9 protects mouse eggs from aneuploidy by controlling microtubule dynamics via Survivin

Biochim Biophys Acta. 2016 Dec;1863(12):2934-2941. doi: 10.1016/j.bbamcr.2016.09.017. Epub 2016 Sep 24.

Abstract

The Cullin9 gene encodes a putative E3 ligase that serves a wide variety of biological functions in mitosis, whereas its roles in meiosis have not yet clearly defined. Here, we report that Cullin9 accumulates on the spindle apparatus and colocalizes with the microtubule fibers during mouse oocyte meiotic maturation. Depletion of Cullin9 by morpholino microinjection results in a remarkably higher rate of disorganized spindles and misaligned chromosomes in oocytes, which is coupled with the impaired kinetochore-microtubule attachments. Resultantly, the incidence of aneuploid eggs significantly increases in Cullin9-depleted oocytes. Moreover, we show that Cullin9 controls Survivin's protein level during meiotic maturation, and thus regulates microtubule stability in oocytes. Thus, our study assigns a new meiotic function to Cullin9 and reveals that it prevents mouse eggs from aneuploidy by regulating microtubule dynamics via Survivin.

Keywords: Aneuploid eggs; Chromosome alignment; Cullin9; Microtubule dynamics; Mouse oocytes; Spindle assembly; Survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Animals
  • Chromosomes, Mammalian / chemistry*
  • Chromosomes, Mammalian / metabolism
  • Cullin Proteins / antagonists & inhibitors
  • Cullin Proteins / genetics*
  • Cullin Proteins / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Kinetochores / metabolism
  • Kinetochores / ultrastructure
  • Meiosis*
  • Mice
  • Microinjections
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Morpholinos / genetics
  • Morpholinos / metabolism
  • Nocodazole / pharmacology
  • Oocytes / cytology
  • Oocytes / growth & development
  • Oocytes / metabolism
  • Oogenesis / genetics
  • Ovum / cytology
  • Ovum / growth & development
  • Ovum / metabolism*
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / ultrastructure
  • Survivin
  • Tubulin Modulators / pharmacology

Substances

  • Birc5 protein, mouse
  • CUL9 protein, mouse
  • Cullin Proteins
  • Inhibitor of Apoptosis Proteins
  • Morpholinos
  • Repressor Proteins
  • Survivin
  • Tubulin Modulators
  • Nocodazole