Kin I Kinesins Are Microtubule-Destabilizing Enzymes

Desai, Arshad; Verma, Suzie; Mitchison, Timothy J.; Walczak, Claire

doi:10.1016/s0092-8674(00)80960-5

Cited by 673 publications

(690 citation statements)

References 44 publications

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“…First, as reported here, the minimal catalytic core of NOD does not have the appropriate properties to suggest minus-end-directed motility. Second, XKCM1 which, like NOD, also does not appear to have motile properties, does label microtubule ends in a manner similar to that observed for NOD:kin:␤-gal by Clark (1997) and Desai et al (1999). Finally, the NOD:kin:␤-gal fusion consisted of the minimal catalytic core of NOD, plus two additional amino acids, fused to the neck linker of Drosophila kinesin (i.e., a chimeric neck).…”

Section: Nod Is Unlikely To Function As a Motormentioning

confidence: 68%

“…This glutamate has been found to stabilize the second arginine via a salt bridge Sablin et al, 1996;Sack et al, 1997). Moreover, the microtubule-depolymerizing Ikins, at least some of which also lack demonstrable in vitro motility (Desai et al, 1999), have a charged residue in the X position, as does NOD.…”

Section: Conserved Residues For Adenine Binding That Are Required Formentioning

confidence: 99%

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Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

Matthies

Baskin

Hawley

2001

MBoC

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NOD is a Drosophila chromosome-associated kinesin-like protein that does not fall into the chromokinesin subfamily. Although NOD lacks residues known to be critical for kinesin function, we show that microtubules activate the ATPase activity of NOD Ͼ2000-fold. Biochemical and genetic analysis of two genetically identified mutations of NOD (NOD DTW and NOD "DR2" ) demonstrates that this allosteric activation is critical for the function of NOD in vivo. However, several lines of evidence indicate that this ATPase activity is not coupled to vectorial transport, including 1) NOD does not produce microtubule gliding; and 2) the substitution of a single amino acid in the Drosophila kinesin heavy chain with the analogous amino acid in NOD results in a drastic inhibition of motility. We suggest that the microtubule-activated ATPase activity of NOD provides transient attachments of chromosomes to microtubules rather than producing vectorial transport.

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Section: Nod Is Unlikely To Function As a Motormentioning

confidence: 68%

Section: Conserved Residues For Adenine Binding That Are Required Formentioning

confidence: 99%

Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

Matthies

Baskin

Hawley

2001

MBoC

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“…Furthermore, Klp5p and Klp6p share with Kip3p an activity that fosters microtubule disassembly, as evidenced by the unusually long and/or robust microtubules found in null mutants (Figures 3-6) (Cottingham and Hoyt, 1997;DeZwaan et al, 1997;Miller et al, 1998). Microtubule-disassembling activity has also been described for the KinI kinesin subfamily (XKCM1, Walczak et al, 1996;MCAK, Maney et al, 1998;Desai et al, 1999) and for Kar3p (Endow et al, 1994). There is, however, no obvious sequence similarity between members of the KIP3 subfamily and the other kinesins with "exotubulase" activity.…”

Section: Kip3 Kinesin Subfamilymentioning

confidence: 84%

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

West

Malmstrom

Troxell

et al. 2001

MBoC

143

175

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The kinesin superfamily of microtubule motor proteins is important in many cellular processes, including mitosis and meiosis, vesicle transport, and the establishment and maintenance of cell polarity. We have characterized two related kinesins in fission yeast, klp5 ϩ and klp6 ϩ , that are amino-terminal motors of the KIP3 subfamily. Analysis of null mutants demonstrates that neither klp5 ϩ nor klp6 ϩ , individually or together, is essential for vegetative growth, although these mutants have altered microtubule behavior. klp5⌬ and klp6⌬ are resistant to high concentrations of the microtubule poison thiabendazole and have abnormally long cytoplasmic microtubules that can curl around the ends of the cell. This phenotype is greatly enhanced in the cell cycle mutant cdc25-22, leading to a bent, asymmetric cell morphology as cells elongate during cell cycle arrest. Klp5p-GFP and Klp6p-GFP both localize to cytoplasmic microtubules throughout the cell cycle and to spindles in mitosis, but their localizations are not interdependent. During the meiotic phase of the life cycle, both of these kinesins are essential. Spore viability is low in homozygous crosses of either null mutant. Heterozygous crosses of klp5⌬ with klp6⌬ have an intermediate viability, suggesting cooperation between these proteins in meiosis.

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“…These include members of the kinesin-13 family (Kif2A, Kif2B, and MCAK/Kif2C), which seem to be strictly MT-depolymerizing enzymes (Desai et al, 1999;Hunter et al, 2003;Helenius et al, 2006), as well as members of the Kinesin-8 family, which are MT plus end-directed motors and plus end-specific depolymerases (Gupta et al, 2006;Howard and Hyman, 2007;Mayr et al, 2007;Varga et al, 2008). MCAK has been shown to be a critical regulator of MT dynamics and organization in vitro, in Xenopus egg extracts and in mammalian cells (Walczak et al, 1996;Desai et al, 1999;Maney et al, 2001;Kline-Smith and Walczak, 2002;Cassimeris and Morabito, 2004;Zhu et al, 2005;Stout et al, 2006;Manning et al, 2007;Ohi et al, 2007;Wordeman et al, 2007;Hedrick et al, 2008). In addition, the action of MCAK is critical at the kinetochore in which it may promote error correction by facilitating kinetochore MT turnover and the coordination of chromosome movement .…”

Section: Introductionmentioning

confidence: 99%

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

Rizk

Bohannon

Wetzel

et al. 2009

MBoC

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Within the mitotic spindle, there are multiple populations of microtubules with different turnover dynamics, but how these different dynamics are maintained is not fully understood. MCAK is a member of the kinesin-13 family of microtubule-destabilizing enzymes that is required for proper establishment and maintenance of the spindle. Using quantitative immunofluorescence and fluorescence recovery after photobleaching, we compared the differences in spindle organization caused by global suppression of microtubule dynamics, by treating cells with low levels of paclitaxel, versus specific perturbation of spindle microtubule subsets by MCAK inhibition. Paclitaxel treatment caused a disruption in spindle microtubule organization marked by a significant increase in microtubules near the poles and a reduction in K-fiber fluorescence intensity. This was correlated with a faster t 1/2 of both spindle and K-fiber microtubules. In contrast, MCAK inhibition caused a dramatic reorganization of spindle microtubules with a significant increase in astral microtubules and reduction in K-fiber fluorescence intensity, which correlated with a slower t 1/2 of K-fibers but no change in the t 1/2 of spindle microtubules. Our data support the model that MCAK perturbs spindle organization by acting preferentially on a subset of microtubules, and they support the overall hypothesis that microtubule dynamics is differentially regulated in the spindle. INTRODUCTIONThe cytoskeleton must undergo dramatic reorganization as cells transition from interphase to mitosis to assemble the mitotic spindle. The spindle is a macromolecular structure composed of a dynamic array of microtubules (MTs) and their associated proteins that is necessary for proper chromosome segregation (Compton, 2000;Walczak and Heald, 2008). At the onset of mitosis, there is an increase in MT turnover that allows for breakdown of the interphase array and assembly of the mitotic spindle (Saxton et al., 1984;. This change is correlated with an increased catastrophe frequency (transition from growth to shrinkage) and a decreased rescue frequency (transition from shrinkage to growth) (Belmont et al., 1990;Gliksman et al., 1992;Verde et al., 1992;Rusan et al., 2001). The changes in MT dynamics are also correlated with a change in MT polymer levels during mitosis (Zhai et al., 1996). At nuclear envelope breakdown, there is a dramatic decrease in MT polymer levels, which may allow the cell to rapidly assemble a mitotic spindle because the released tubulin dimers can polymerize into new spindle MTs. As the cell progresses from mitosis to the next interphase, there is no change in the levels of MT polymer (Zhai et al., 1996), suggesting that MT polymer gets reorganized to reform the interphase MT cytoskeleton, without a significant change in the dynamics of the MTs. These studies highlight the need for the cell to possess a mechanism to temporally regulate MT dynamics.In addition to the temporal changes in dynamics throughout the cell cycle, the dynamics of MTs within mitosis are also...

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Kin I Kinesins Are Microtubule-Destabilizing Enzymes

Cited by 673 publications

References 44 publications

Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

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Kin I Kinesins Are Microtubule-Destabilizing Enzymes

Cited by 673 publications

References 44 publications

Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

Two Related Kinesins,klp5+andklp6+, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

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Product

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Two Related Kinesins,klp5⁺andklp6⁺, Foster Microtubule Disassembly and Are Required for Meiosis in Fission Yeast