Cell and Molecular Biology of the Spindle Matrix

Johansen, Kristen M.

doi:10.1016/s0074-7696(07)63004-6

Cited by 57 publications

(73 citation statements)

References 306 publications

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Section: Introductionmentioning

confidence: 90%

“…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: 90%

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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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Section: Introductionmentioning

confidence: 90%

mentioning

confidence: 90%

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

Brust‐Mascher

Sommi

Cheerambathur

et al. 2009

MBoC

109

128

View full text Add to dashboard Cite

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“…The spindle matrix is hypothesized to provide a stationary or elastic molecular matrix that can provide a substrate for motor molecules to interact with during microtubule sliding and that can stabilize the spindle during force production (Pickett-Heaps et al, 1997;Forer et al, 2008). During mitosis, the Megator-defined spindle matrix forms a fusiform spindle-like structure that is co-aligned with the microtubule-based spindle apparatus and that persists in the absence of microtubules (reviewed in Johansen and Johansen, 2007). Asator transcript levels from all three isoforms were determined by qRT-PCR and normalized to the mRNA levels of the microtubule associated motor protein Ncd.…”

Section: Discussionmentioning

confidence: 99%

“…This complex forms a fusiform spindle structure that persists in the absence of polymerized tubulin and, based on theoretical considerations of the requirements for force production, has been proposed to help support the microtubule spindle apparatus during mitosis (reviewed in Johansen and Johansen, 2007). While Skeletor, Chromator, and EAST appear to have no obvious mammalian homologs, Megator is a 260-kD protein with a large NH 2 -terminal coiled-coil domain and a shorter COOH-terminal acidic region that shows overall structural and sequence similarity to the mammalian nuclear pore complex Tpr protein (Zimowska et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Asator, a tau‐tubulin kinase homolog in Drosophila localizes to the mitotic spindle

Yao

Cai

et al. 2009

Developmental Dynamics

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We have used a yeast two-hybrid interaction assay to identify Asator, a tau-tubulin kinase homolog in Drosophila that interacts directly with the spindle matrix protein Megator. Using immunocytochemical labeling by an Asator-specific mAb as well as by transgenic expression of a GFP-labeled Asator construct, we show that Asator is localized to the cytoplasm during interphase but redistributes to the spindle region during mitosis. Determination of transcript levels using qRT-PCR suggested that Asator is expressed throughout development but at relatively low levels. By P-element excision, we generated a null or strong hypomorphic Asator exc allele that resulted in complete adult lethality when homozygous, indicating that Asator is an essential gene. That the observed lethality was caused by impaired Asator function was further supported by the partial restoration of viability by transgenic expression of Asator-GFP in the Asator exc homozygous mutant background. The finding that Asator localizes to the spindle region during mitosis and directly can interact with Megator suggests that its kinase activity may be involved in regulating microtubule dynamics and microtubule spindle function. Developmental Dynamics 238:3248-3256,

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“…Several candidates have been proposed to form a non-microtubular spindle matrix but evidence for a direct role in anaphase remains controversial [189]. In Drosophila, a widely conserved protein, Megator, has been recently implicated in anaphase chromosome movement [190], through a specific role in spindle elongation.…”

Section: The Spindle Matrixmentioning

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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Cell and Molecular Biology of the Spindle Matrix

Cited by 57 publications

References 306 publications

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

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

Asator, a tau‐tubulin kinase homolog in Drosophila localizes to the mitotic spindle

The perpetual movements of anaphase

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