title: HURP permits MTOC sorting for robust meiotic spindle bipolarity, similar to extra centrosome clustering in cancer cells.
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.
authors.affiliation: Unité Mixte de Recherche 7622, Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Breuer
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kolano
authors.forename: Mijung
authors.initials: M
authors.lastname: Kwon
authors.forename: Chao-Chin
authors.initials: CC
authors.lastname: Li
authors.forename: Ting-Fen
authors.initials: TF
authors.lastname: Tsai
authors.forename: David
authors.initials: D
authors.lastname: Pellman
authors.forename: Stéphane
authors.initials: S
authors.lastname: Brunet
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Verlhac
mesh_terms: D000705:Anaphase / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D009865:Oocytes / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C522423:EB3 protein, mouse; C532763:HURP protein, mouse; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D016547:Kinesins