HURP permits MTOC sorting for robust meiotic spindle bipolarity, similar to extra centrosome clustering in cancer cells

J Cell Biol. 2010 Dec 27;191(7):1251-60. doi: 10.1083/jcb.201005065. Epub 2010 Dec 20.

Abstract

In contrast to somatic cells, formation of acentriolar meiotic spindles relies on the organization of microtubules (MTs) and MT-organizing centers (MTOCs) into a stable bipolar structure. The underlying mechanisms are still unknown. We show that this process is impaired in hepatoma up-regulated protein (Hurp) knockout mice, which are viable but female sterile, showing defective oocyte divisions. HURP accumulates on interpolar MTs in the vicinity of chromosomes via Kinesin-5 activity. By promoting MT stability in the spindle central domain, HURP allows efficient MTOC sorting into distinct poles, providing bipolarity establishment and maintenance. Our results support a new model for meiotic spindle assembly in which HURP ensures assembly of a central MT array, which serves as a scaffold for the genesis of a robust bipolar structure supporting efficient chromosome congression. Furthermore, HURP is also required for the clustering of extra centrosomes before division, arguing for a shared molecular requirement of MTOC sorting in mammalian meiosis and cancer cell division.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / genetics
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Centrosome / metabolism*
  • Chromosome Segregation / genetics
  • Female
  • Gene Expression / genetics
  • Humans
  • Kinesins / antagonists & inhibitors
  • Kinesins / metabolism
  • Kinetochores / metabolism
  • Meiosis / physiology*
  • Mice
  • Mice, 129 Strain
  • Mice, Knockout
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Organizing Center / metabolism*
  • Microtubules / metabolism
  • Mitosis / physiology*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Oocytes / metabolism
  • RNA, Small Interfering / genetics
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*

Substances

  • Cell Cycle Proteins
  • EB3 protein, mouse
  • HURP protein, mouse
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Kinesins