Genes Required for Mitotic Spindle Assembly in
            <i>Drosophila</i>
            S2 Cells

Goshima, Gohta; Wollman, Roy; Goodwin, Sarah S.; Zhang, Nan; Scholey, Jonathan M.; Vale, Ronald D.; Stuurman, Nico

doi:10.1126/science.1141314

Cited by 508 publications

(637 citation statements)

References 36 publications

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“…Transcriptional profiling showed that 107 genes were differentially expressed between diploid and tetraploid Rat1a-GpIba cells. Although it seems likely that this group plays a role in promoting, maintaining or responding to tetraploidy, it was notable for its lack of genes functioning in homologous recombination, sister chromatid cohesion or mitotic spindle function, which are implicated in the survival of yeast tetraploids and in the assembly of Drosophila mitotic spindles (Storchova et al, 2006;Goshima et al, 2007). This discrepancy may reflect more the way by which these critical genes were identified than in actual functional differences.…”

Section: Discussionmentioning

confidence: 99%

Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibα

Cohen

et al. 2007

Oncogene

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GpIba, a subunit of the von Willebrand factor receptor, functions during blood clotting to promote platelet adhesion and activation. GpIba is widely expressed, is positively regulated by c-Myc and is essential for the promotion of c-Myc-mediated chromosomal instability. We now show that GpIba is also a classical oncoprotein in which its deregulated expression leads to transformation, reduced growth factor requirements, increased resistance to apoptosis, and, in primary cells, p53-dependent senescence. Finally, GpIba also promotes double-stranded DNA breaks, and induces profound nuclear dysmorphology, indicating that, in addition to its direct transforming function, it displays genotoxicity at several distinct levels. These findings identify novel functions for GpIba and pathways through which c-Myc mediates transformation and global genomic destabilization.

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Section: Discussionmentioning

confidence: 99%

Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibα

Cohen

et al. 2007

Oncogene

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“…Fifth, specific gene silencing can be easily achieved by RNA interference (RNAi), by simply adding dsRNA to the culture medium (13). This is particularly useful for high-throughput genome-wide screenings, which are now well established (14)(15)(16). One major disadvantage though, has been related with the fact that most Drosophila cell lines are semi-adherent and thus cells are round, making highresolution microscopy difficult.…”

Section: Introductionmentioning

confidence: 99%

Dissecting Mitosis with Laser Microsurgery and RNAi in Drosophila Cells

Pereira

Matos

Lince-Faria

et al. 2009

Methods in Molecular Biology

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Progress from our present understanding of the mechanisms behind mitosis has been compromised by the fact that model systems that were ideal for molecular and genetic studies (such as yeasts, C. elegans or Drosophila) were not suitable for intracellular micromanipulation. Unfortunately, those systems that were appropriate for micromanipulation (like newt lung cells, PtK1 cells or insect spermatocytes) are not amenable for molecular studies. We believe that we can significantly broaden this scenario by developing high resolution live cell microscopy tools in a system where micromanipulation studies could be combined with modern gene-interference

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Brust‐Mascher

Sommi

Cheerambathur

et al. 2009

MBoC

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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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Genes Required for Mitotic Spindle Assembly in Drosophila S2 Cells

Cited by 508 publications

References 36 publications

Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibα

Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibα

Dissecting Mitosis with Laser Microsurgery and RNAi in Drosophila Cells

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

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