title: Mammalian CLASP1 and CLASP2 cooperate to ensure mitotic fidelity by regulating spindle and kinetochore function.
abstract: CLASPs are widely conserved microtubule plus-end-tracking proteins with essential roles in the local regulation of microtubule dynamics. In yeast, Drosophila, and Xenopus, a single CLASP orthologue is present, which is required for mitotic spindle assembly by regulating microtubule dynamics at the kinetochore. In mammals, however, only CLASP1 has been directly implicated in cell division, despite the existence of a second paralogue, CLASP2, whose mitotic roles remain unknown. Here, we show that CLASP2 localization at kinetochores, centrosomes, and spindle throughout mitosis is remarkably similar to CLASP1, both showing fast microtubule-independent turnover rates. Strikingly, primary fibroblasts from Clasp2 knockout mice show numerous spindle and chromosome segregation defects that can be partially rescued by ectopic expression of Clasp1 or Clasp2. Moreover, chromosome segregation rates during anaphase A and B are slower in Clasp2 knockout cells, which is consistent with a role of CLASP2 in the regulation of kinetochore and spindle function. Noteworthy, cell viability/proliferation and spindle checkpoint function were not impaired in Clasp2 knockout cells, but the fidelity of mitosis was strongly compromised, leading to severe chromosomal instability in adult cells. Together, our data support that the partial redundancy of CLASPs during mitosis acts as a possible mechanism to prevent aneuploidy in mammals.
authors.affiliation: Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Pereira
authors.forename: António J
authors.initials: AJ
authors.lastname: Pereira
authors.forename: Ana R R
authors.initials: AR
authors.lastname: Maia
authors.forename: Ksenija
authors.initials: K
authors.lastname: Drabek
authors.forename: C Laura
authors.initials: CL
authors.lastname: Sayas
authors.forename: Polla J
authors.initials: PJ
authors.lastname: Hergert
authors.forename: Mariana
authors.initials: M
authors.lastname: Lince-Faria
authors.forename: Irina
authors.initials: I
authors.lastname: Matos
authors.forename: Cristina
authors.initials: C
authors.lastname: Duque
authors.forename: Tatiana
authors.initials: T
authors.lastname: Stepanova
authors.forename: Conly L
authors.initials: CL
authors.lastname: Rieder
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.forename: Helder
authors.initials: H
authors.lastname: Maiato
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D008938:Mitosis; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection
chemical_list: C497850:CLASP1 protein, human; C497851:CLASP2 protein, human; D008869:Microtubule-Associated Proteins