Kinesin-related proteins required for structural integrity of the mitotic spindle

Saunders, William S.; Hoyt, M. Andrew

doi:10.1016/0092-8674(92)90169-d

Cited by 367 publications

(401 citation statements)

References 24 publications

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“…This suggests that kinesin-5 may normally contribute to spindle bipolarity by sliding apart interpolar (ip) MTs to drive spindle pole separation during mitotic spindle assembly, elongation and function. (Saunders and Hoyt, 1992;Sawin et al, 1992;Heck et al, 1993;Saunders et al, 1997;Straight et al, 1998;Walczak et al, 1998;Sharp et al, 2000a;Brust-Mascher and Scholey, 2002;Brust-Mascher et al, 2004;Cheerambathur et al, 2007). It is clear that this activity is deployed differently in different systems, however.…”

Section: Introductionmentioning

confidence: 99%

“…The most obvious and frequently observed consequence of loss of activity of kinesin-5 motors, induced by loss-offunction mutation, antibody inhibition, small molecule inhibition, or RNA interference, is the formation of abnormal monoastral spindles (Enos and Morris, 1990;Saunders and Hoyt, 1992;Sawin et al, 1992;Heck et al, 1993;Saunders et al, 1997;Cottingham et al, 1999;Mayer et al, 1999;Sharp et al, 1999b;Sharp et al, 2000a;Goshima and Vale, 2003). This suggests that kinesin-5 may normally contribute to spindle bipolarity by sliding apart interpolar (ip) MTs to drive spindle pole separation during mitotic spindle assembly, elongation and function.…”

Section: Introductionmentioning

confidence: 99%

“…It is clear that this activity is deployed differently in different systems, however. For example, kinesin-5 activity is required for initial spindle assembly in yeast but not in Drosophila embryos, whereas it is required for spindle maintenance in both systems (Saunders and Hoyt, 1992;Sharp et al, 1999b). Inhibition of kinesin-5 in different systems has also resulted in defects in poleward flux (Miyamoto et al, 2004;Cameron et al, 2006) and spindle pole organization (Gaglio et al, 1996).…”

mentioning

confidence: 99%

“…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) and forms presumptive MT-MT cross-bridges (Sharp et al, 1999a). These results suggest that ensembles of multiple kinesin-5 motors could serve as dynamic cross-links that organize spindle MTs into bundles and drive a sliding filament mechanism that pushes apart antiparallel spindle MTs (Sharp et al, 1999a;Brust-Mascher et al, 2004), although alternative mechanisms of action for kinesin-5 motors have also been proposed (Kapoor and Mitchison, 2001;Tsai et al, 2006;Johansen and Johansen, 2007;Gardner et al, 2008).The most obvious and frequently observed consequence of loss of activity of kinesin-5 motors, induced by loss-offunction mutation, antibody inhibition, small molecule inhibition, or RNA interference, is the formation of abnormal monoastral spindles (Enos and Morris, 1990;Saunders and Hoyt, 1992;Sawin et al, 1992;Heck et al, 1993;Saunders et al, 1997;Cottingham et al, 1999;Mayer et al, 1999;Sharp et al, 1999b;Sharp et al, 2000a;Goshima and Vale, 2003). This suggests that kinesin-5 may normally contribute to spindle bipolarity by sliding apart interpolar (ip) MTs to drive spindle pole separation during mitotic spindle assembly, elongation and function.…”

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confidence: 99%

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

Brust‐Mascher

Sommi

Cheerambathur

et al. 2009

MBoC

112

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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Brust‐Mascher

Sommi

Cheerambathur

et al. 2009

MBoC

112

128

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“…Although the poles separate initially, they later slide back together, chromosomes fail to segregate, and the plus ends of the spindle microtubules radiate outward, with the chromosomes arranged in a ring around the edge [Saunders and Hoyt, 1992;Heck et al, 1993;Endow, 1999;Goshima and Vale, 2003]. Evidence of this kind implies that kinesin-5 motor proteins play an indispensable role in stabilizing the spindle midzone and separating spindle halves at anaphase.…”

Section: Kinesin-5 Motor Proteinsmentioning

confidence: 99%

Emerging molecular mechanisms that power and regulate the anastral mitotic spindle of flowering plants

Bannigan

Lizotte-Waniewski

Riley

et al. 2007

Cell Motil. Cytoskeleton

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Flowering plants, lacking centrosomes as well as dynein, assemble their mitotic spindle via a pathway that is distinct visually and molecularly from that of animals and yeast. The molecular components underlying mitotic spindle assembly and function in plants are beginning to be discovered. Here, we review recent evidence suggesting the preprophase band in plants functions analogously to the centrosome in animals in establishing spindle bipolarity, and we review recent progress characterizing the roles of specific motor proteins in plant mitosis. Loss of function of certain minus-end-directed KIN-14 motor proteins causes a broadening of the spindle pole; whereas, loss of function of a KIN-5 causes the formation of monopolar spindles, resembling those formed when the homologous motor protein (e.g., Eg5) is knocked out in animal cells. We present a phylogeny of the kinesin-5 motor domain, which shows deep divergence among plant sequences, highlighting possibilities for specialization. Finally, we review information concerning the roles of selected structural proteins at mitosis as well as recent findings concerning regulation of M-phase in plants. Insight into the mitotic spindle will be obtained through continued comparison of mitotic mechanisms in a diversity of cells. Cell Motil. Cytoskeleton 65: 1-11, 2008. '

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Review: An Overview of theSaccharomyces cerevisiae Microtubule and Microfilament Cytoskeleton

Winsor

Schiebel

1997

Yeast

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Kinesin-related proteins required for structural integrity of the mitotic spindle

Cited by 367 publications

References 24 publications

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

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

Emerging molecular mechanisms that power and regulate the anastral mitotic spindle of flowering plants

Review: An Overview of theSaccharomyces cerevisiae Microtubule and Microfilament Cytoskeleton

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