Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly
Open Access
- 20 November 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 27 (24), 3235-3245
- https://doi.org/10.1038/emboj.2008.242
Abstract
Bipolar spindle assembly critically depends on the microtubule plus‐end‐directed motor Eg5 that binds antiparallel microtubules and slides them in opposite directions. As such, Eg5 can produce the necessary outward force within the spindle that drives centrosome separation and inhibition of this antiparallel sliding activity results in the formation of monopolar spindles. Here, we show that upon depletion of the minus‐end‐directed motor dynein, or the dynein‐binding protein Lis1, bipolar spindles can form in human cells with substantially less Eg5 activity, suggesting that dynein and Lis1 produce an inward force that counteracts the Eg5‐dependent outward force. Interestingly, we also observe restoration of spindle bipolarity upon depletion of the microtubule plus‐end‐tracking protein CLIP‐170. This function of CLIP‐170 in spindle bipolarity seems to be mediated through its interaction with dynein, as loss of CLIP‐115, a highly homologous protein that lacks the dynein–dynactin interaction domain, does not restore spindle bipolarity. Taken together, these results suggest that complexes of dynein, Lis1 and CLIP‐170 crosslink and slide microtubules within the spindle, thereby producing an inward force that pulls centrosomes together.This publication has 50 references indexed in Scilit:
- Poleward transport of Eg5 by dynein–dynactin in Xenopus laevis egg extract spindlesThe Journal of cell biology, 2008
- The Kinesin-13 Proteins Kif2a, Kif2b, and Kif2c/MCAK Have Distinct Roles during Mitosis in Human CellsMolecular Biology of the Cell, 2007
- Kinetochore Dynein Is Required for Chromosome Motion and Congression Independent of the Spindle CheckpointCurrent Biology, 2007
- Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cellsThe EMBO Journal, 2006
- Roles of Polymerization Dynamics, Opposed Motors, and a Tensile Element in Governing the Length ofXenopusExtract Meiotic SpindlesMolecular Biology of the Cell, 2005
- The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinksNature, 2005
- The KinI kinesin Kif2a is required for bipolar spindle assembly through a functional relationship with MCAKThe Journal of cell biology, 2004
- Formation of Spindle Poles by Dynein/Dynactin-Dependent Transport of NumaThe Journal of cell biology, 2000
- A Complex of NuMA and Cytoplasmic Dynein Is Essential for Mitotic Spindle AssemblyCell, 1996
- Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivoCell, 1995