Kinesin-5 acts as a brake in anaphase spindle elongation

Saunders, Adam; Powers, James; Strome, Susan; Saxton, William M.

doi:10.1016/j.cub.2007.05.001

Cited by 127 publications

(163 citation statements)

References 13 publications

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“…Current models require that these motors slide apart anti-parallel spindle microtubules, generating an outward pushing force on the spindle poles 8 . However, in worms the kinesin-5 operates as a brake to limit spindle elongation (which is driven by astral-microtubule pulling at the cell cortex) 151 . As for centrosome separation, kinesin-5 family members clearly generate both driving and braking forces during anaphase to modulate the rate at which microtubules slide apart.…”

Section: Anaphase Chromosome Movementmentioning

confidence: 99%

Prime movers: the mechanochemistry of mitotic kinesins

Cross

McAinsh

2014

Nat Rev Mol Cell Biol

187

203

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Section: Anaphase Chromosome Movementmentioning

confidence: 99%

Prime movers: the mechanochemistry of mitotic kinesins

Cross

McAinsh

2014

Nat Rev Mol Cell Biol

187

203

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“…However, in Dictyostelium amoebae and C. elegans embryos, kinesin-5 motors play relatively minor mitotic roles, and they appear to be dispensable for mitosis (Saunders et al, 2007;Tikhonenko et al, 2008). Thus, mitotic motors can be deployed to carry out very different functions in different types of spindles, presenting a challenge for the formulation of general, integrated models of kinesin-5 function.…”

Section: Relation To Experimental Studies Of Kinesin-5 Function In Otmentioning

confidence: 99%

“…However, in Drosophila S2 cells, perturbation of kinesin-5 levels did not interfere with metaphase spindle length (Goshima et al, 2005b). In Caenorhabditis elegans, kinesin-5 was also found to exert a braking effect on the spindle midzone that governs the rate of spindle elongation mediated by cortical motors (Saunders et al, 2007). It is unclear if these findings are relevant to all spindles and if they all reflect the antiparallel MT sliding activity of kinesin-5, or if kinesin-5 functions differently in different systems as implied by the proposal that kinesin-5 functions as a MT depolymerase rather than a sliding motor to control chromosome congression in Saccharomyces cerevisiae (Gardner et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

Kinesin-5–dependent Poleward Flux and Spindle Length Control inDrosophilaEmbryo Mitosis

Brust‐Mascher

Sommi

Cheerambathur

et al. 2009

MBoC

109

128

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We used antibody microinjection and genetic manipulations to dissect the various roles of the homotetrameric kinesin-5, KLP61F, in astral, centrosome-controlled Drosophila embryo spindles and to test the hypothesis that it slides apart interpolar (ip) microtubules (MT), thereby controlling poleward flux and spindle length. In wild-type and Ncd null mutant embryos, anti-KLP61F dissociated the motor from spindles, producing a spatial gradient in the KLP61F content of different spindles, which was visible in KLP61F-GFP transgenic embryos. The resulting mitotic defects, supported by gene dosage experiments and time-lapse microscopy of living klp61f mutants, reveal that, after NEB, KLP61F drives persistent MT bundling and the outward sliding of antiparallel MTs, thereby contributing to several processes that all appear insensitive to cortical disruption. KLP61F activity contributes to the poleward flux of both ipMTs and kinetochore MTs and to the length of the metaphase spindle. KLP61F activity maintains the prometaphase spindle by antagonizing Ncd and another unknown force-generator and drives anaphase B, although the rate of spindle elongation is relatively insensitive to the motor's concentration. Finally, KLP61F activity contributes to normal chromosome congression, kinetochore spacing, and anaphase A rates. Thus, a KLP61F-driven sliding filament mechanism contributes to multiple aspects of mitosis in this system. INTRODUCTIONMitosis, the process by which identical copies of the replicated genome are distributed to the products of each cell division, involves a highly dynamic sequence of coordinated motility events, mediated by a bipolar protein machine, the mitotic spindle (Karsenti and Vernos, 2001;Mitchison and Salmon, 2001;Gadde and Heald, 2004;Wadsworth and Khodjakov, 2004;Mogilner et al., 2006;Brust-Mascher and Scholey, 2007;Walczak and Heald, 2008). These motility events are driven by molecular-scale forces generated by mitotic kinesins and dyneins, together with dynamic microtubules (MTs), whose activities are controlled by a network of regulatory proteins, e.g., mitotic kinases, phosphatases, and proteolytic enzymes (Sharp et al., 2000c; BettencourtDias et al., 2004;Maiato and Sunkel, 2004;Rogers et al., 2005;Goshima et al., 2007). Among these mitotic proteins, the kinesin-5 motor is thought to play a key role (Cottingham et al., 1999;Valentine et al., 2006a;Civelekoglu-Scholey and Scholey, 2007).Purified kinesin-5 is a slow, modestly processive, plusend-directed bipolar homotetramer capable of cross-linking adjacent MTs and sliding apart antiparallel MTs in motility assays (Sawin et al., 1992;Cole et al., 1994;Kashina et al., 1996a;Kapitein et al., 2005;Tao et al., 2006;Valentine et al., 2006b;Krzysiak et al., 2008;Van den Wildenberg et al., 2008). In yeast cells the homotetrameric structure of kinesin-5 appears to be essential for mitosis (Hildebrandt et al., 2006), and in Drosophila embryos KLP61F displays dynamic properties consistent with an association with spindle MTs (Cheerambathur et al., 2008) ...

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“…Cytoplasmic dynein located at the cell cortex has been implicated in this astral MT pulling mechanism [89,90,96,[233][234][235]. On the other hand, proteins required for microtubule polymerization and growth/stabilization of interpolar microtubules [236], such as CLASPs [219], coordinated with the activity of kinesin-5 at the spindle midzone, might work as governors [237].…”

Section: Anaphase a Vs Anaphase Bmentioning

confidence: 99%

The perpetual movements of anaphase

Maiato

Lince-Faria

2010

Cell. Mol. Life Sci.

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One of the most extraordinary events in the lifetime of a cell is the coordinated separation of sister chromatids during cell division. This is truly the essence of the entire mitotic process and the reason for the most profound morphological changes in cytoskeleton and nuclear organization that a cell may ever experience. It all occurs within a very short time window known as "anaphase", as if the cell had spent the rest of its existence getting ready for this moment in an ultimate act of survival. And there is a good reason for this: no space for mistakes. Problems in the distribution of chromosomes during cell division have been correlated with aneuploidy, a common feature observed in cancers and several birth defects, and the main cause of spontaneous abortion in humans. In this paper we critically review the mechanisms of anaphase chromosome motion that resisted the scrutiny of more than one hundred years of research as part of a tribute to the pioneering work of Miguel Mota.

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Kinesin-5 acts as a brake in anaphase spindle elongation

Cited by 127 publications

References 13 publications

Prime movers: the mechanochemistry of mitotic kinesins

Prime movers: the mechanochemistry of mitotic kinesins

Kinesin-5–dependent Poleward Flux and Spindle Length Control inDrosophilaEmbryo Mitosis

The perpetual movements of anaphase

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