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

Author:

Breuer Manuel1,Kolano Agnieszka1,Kwon Mijung2,Li Chao-Chin3,Tsai Ting-Fen3,Pellman David2,Brunet Stéphane1,Verlhac Marie-Hélène1

Affiliation:

1. Unité Mixte de Recherche 7622, Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, 75005 Paris, France

2. Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115

3. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan

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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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