title: SKAP, an outer kinetochore protein, is required for mouse germ cell development.
abstract: In sexually reproducing organisms, accurate gametogenesis is crucial for the transmission of genetic material from one generation to the next. This requires the faithful segregation of chromosomes during mitotic and meiotic divisions. One of the main players in this process is the kinetochore, a large multi-protein complex that forms at the interface of centromeres and microtubules. Here, we analyzed the expression profile and function of small kinetochore-associated protein (SKAP) in the mouse. We found that two distinct SKAP isoforms are specifically expressed in the germline: a smaller isoform, which is detected in spermatogonia and spermatocytes and localized in the outer mitotic and meiotic kinetochores from metaphase to telophase, and a larger isoform, which is expressed in the cytoplasm of elongating spermatids. We generated SKAP-deficient mice and found that testis size and sperm production were severely reduced in mutant males. This phenotype was partially caused by defects during spermatogonia proliferation before entry into meiosis. We conclude that mouse SKAP, while being dispensable for somatic cell divisions, has an important role in the successful outcome of male gametogenesis. In germ cells, analogous to what has been suggested in studies using immortalized cells, SKAP most likely stabilizes the interaction between kinetochores and microtubules, where it might be needed as an extra safeguard to ensure the correct segregation of mitotic and meiotic chromosomes.
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain corinne.grey@igh.cnrs.fr bernard.de-massy@igh.cnrs.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Grey
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Julien
authors.initials: J
authors.lastname: Espeut
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ametsitsi
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Luksza
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Christine
authors.initials: C
authors.lastname: Brun
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Marie-Hélene
authors.initials: MH
authors.lastname: Verlhac
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: José Angél
authors.initials: JA
authors.lastname: Suja
authors.affiliation: CNRSIGH (UPR1142), 141 rue de la Cardonille, 34396 Montpellier, FranceCNRSCRBM (UMR5237), 1919 route de Mende, 34293 Montpellier, FranceINRADépartement Biologie et Amélioration des Plantes, route de Saint-Cyr, 78026 Versailles, FranceCollège de FranceCIRB (UMR CNRS 7241/INSERM- U1050), 11 Place Marcelin Berthelot, 75005 Paris, FranceDepartamento de BiologíaFacultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain corinne.grey@igh.cnrs.fr bernard.de-massy@igh.cnrs.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: de Massy
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D005298:Fertility; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008938:Mitosis; D013091:Spermatogenesis; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C000612101:SKAP protein, mouse