title: Mps1 at kinetochores is essential for female mouse meiosis I.
abstract: In female meiosis, chromosome missegregations lead to the generation of aneuploid oocytes and can cause the development of trisomies or infertility. Because mammalian female meiosis I is error prone, the full functionality of control mechanisms, such as the spindle assembly checkpoint (SAC), has been put into question. The SAC monitors the correct orientation, microtubule occupancy and tension on proteinaceous structures named kinetochores. Although it has been shown previously that the SAC exists in meiosis I, where attachments are monopolar, the role of microtubule occupancy for silencing the SAC and the importance of certain essential SAC components, such as the kinase Mps1, are unknown in mammalian oocytes. Using a conditional loss-of-function approach, we address the role of Mps1 in meiotic progression and checkpoint control in meiosis I. Our data demonstrate that kinetochore localization of Mps1 is required for the proper timing of prometaphase and is essential for SAC control, chromosome alignment and aurora C localization in meiosis I. The absence of Mps1 from kinetochores severely impairs chromosome segregation in oocyte meiosis I and, therefore, fertility in mice. In addition, we settle a long-standing question in showing that kinetochore-microtubule attachments are present in prometaphase I at a time when most of the SAC protein Mad2 disappears from kinetochores.
authors.affiliation: UPMC, 9 quai St Bernard, 75005 Paris, France.
authors.forename: Khaled
authors.initials: K
authors.lastname: Hached
authors.forename: Stephanie Z
authors.initials: SZ
authors.lastname: Xie
authors.forename: Eulalie
authors.initials: E
authors.lastname: Buffin
authors.forename: Damien
authors.initials: D
authors.lastname: Cladière
authors.forename: Christophe
authors.initials: C
authors.lastname: Rachez
authors.forename: Marina
authors.initials: M
authors.lastname: Sacras
authors.forename: Peter K
authors.initials: PK
authors.lastname: Sorger
authors.forename: Katja
authors.initials: K
authors.lastname: Wassmann
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D005260:Female; D005455:Fluorescent Antibody Technique; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C441620:Ttk protein, mouse; D017346:Protein Serine-Threonine Kinases