Mammalian CLASP1 and CLASP2 Cooperate to Ensure Mitotic Fidelity by Regulating Spindle and Kinetochore Function
- 1 October 2006
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 17 (10), 4526-4542
- https://doi.org/10.1091/mbc.e06-07-0579
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.Keywords
This publication has 59 references indexed in Scilit:
- Mitotic Checkpoint Slippage in Humans Occurs via Cyclin B Destruction in the Presence of an Active CheckpointCurrent Biology, 2006
- Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cellsThe EMBO Journal, 2006
- Efficient Mitosis in Human Cells Lacking Poleward Microtubule FluxCurrent Biology, 2005
- The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesisGenes & Development, 2005
- Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC The Journal of cell biology, 2003
- KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegansJournal of Bone and Joint Surgery, 2003
- Regulation of microtubule assembly by human EB1 family proteinsOncogene, 2001
- EB3, a novel member of the EB1 family preferentially expressed in the central nervous system, binds to a CNS-specific APC homologueOncogene, 2000
- Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends.The Journal of cell biology, 1987
- A permeabilized cell model for studying cell division: a comparison of anaphase chromosome movement and cleavage furrow constriction in lysed PtK1 cells.The Journal of cell biology, 1981