The<i>Drosophila</i>Kinesin-like Protein KLP67A Is Essential for Mitotic and Male Meiotic Spindle Assembly

Gandhi, Rita; Bonaccorsi, Silvia; Wentworth, Diana; Doxsey, Stephen; Gatti, Maurizio; Pereira, Ana Marta

doi:10.1091/mbc.e03-05-0342

Cited by 74 publications

(84 citation statements)

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“…Double knockout of klp5 ϩ and klp6 ϩ in S. pombe causes chromosome pairs to move back and forth along the spindle for an extended period before sister chromatid separation (Garcia et al, 2002;West et al, 2002). Mutations in the Klp67A gene in Drosophila caused an increase in MT length, formation of disorganized bipolar spindles, abnormal chromosome congression, alignment and segregation, and failure of cytokinesis (Gandhi et al, 2004;Savoian et al, 2004). Our preliminary results indicate that human Kif18 also localizes to the kinetochores and mitotic spindle during early mitosis and translocates to the spindle midzone/midbody during cytokinesis (C. Zhu and W. Jiang, unpublished observations).…”

Section: Discussionmentioning

confidence: 65%

“…Database analysis indicates that Kif18 shares significant sequence homology with the Kip3 subfamily of N-terminal positioned motor kinesins, Kip3 (S. cerevisiae), Klp5/6 (Schizosaccharomyces pombe), KipB (Aspergillus nidulans), and Klp67A (Drosophila) (unpublished data and Cottingham and Hoyt, 1997;Garcia et al, 2002;West et al, 2002;Gandhi et al, 2004;Rischitor et al, 2004;Savoian et al, 2004). Klp5/6, KipB, and Klp67A are involved in spindle formation and chromosome segregation during meiosis and/or mitosis (Garcia et al, 2002;West et al, 2002;Gandhi et al, 2004;Rischitor et al, 2004;Savoian et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Klp5/6, KipB, and Klp67A are involved in spindle formation and chromosome segregation during meiosis and/or mitosis (Garcia et al, 2002;West et al, 2002;Gandhi et al, 2004;Rischitor et al, 2004;Savoian et al, 2004). S. pombe Klp5/6 and Drosophila Klp67A localize to kinetochores and the mitotic spindle in early mitosis and concentrate to the spindle midzone/midbody during cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

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Functional Analysis of Human Microtubule-based Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA Interference

Zhu

Zhao

Bibikova

et al. 2005

MBoC

378

344

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Microtubule (MT)-based motor proteins, kinesins and dyneins, play important roles in multiple cellular processes including cell division. In this study, we describe the generation and use of an Escherichia coli RNase III-prepared human kinesin/dynein esiRNA library to systematically analyze the functions of all human kinesin/dynein MT motor proteins. Our results indicate that at least 12 kinesins are involved in mitosis and cytokinesis. Eg5 (a member of the kinesin-5 family), Kif2A (a member of the kinesin-13 family), and KifC1 (a member of the kinesin-14 family) are crucial for spindle formation; KifC1, MCAK (a member of the kinesin-13 family), CENP-E (a member of the kinesin-7 family), Kif14 (a member of the kinesin-3 family), Kif18 (a member of the kinesin-8 family), and Kid (a member of the kinesin-10 family) are required for chromosome congression and alignment; Kif4A and Kif4B (members of the kinesin-4 family) have roles in anaphase spindle dynamics; and Kif4A, Kif4B, MKLP1, and MKLP2 (members of the kinesin-6 family) are essential for cytokinesis. Using immunofluorescence analysis, time-lapse microscopy, and rescue experiments, we investigate the roles of these 12 kinesins in detail. INTRODUCTIONThe mitotic spindle, a unique cellular apparatus assembled at the beginning of mitosis, plays a pivotal role in regulating mitosis and cytokinesis. Although tubulins are the most abundant protein in the mitotic spindle, many additional proteins are involved in regulating its formation and function. Most prominent among these are members of the kinesin and dynein families of MT-based motor proteins (Mandelkow and Mandelkow, 2002;Vale, 2003), which generate directional movement along microtubules. The kinesin proteins share a conserved, ϳ340 amino acid, motor domain that utilizes ATP to fuel their movement along MTs. Outside the motor domain, kinesins also contain different "stalk" and "tail" domains that mediate oligomerization, regulation of motor activity, and interactions with their specific cargos (Vale, 2003).The roles of kinesins in mitosis and cytokinesis have been extensively studied in Saccharomyces cerevisiae, in which there are six kinesin genes belonging to five subfamilies. Gene disruption experiments have demonstrated that five of these kinesins play essential roles in regulating the formation, orientation, and elongation of the mitotic spindle and the segregation of chromosomes in mitosis (Hildebrandt and Hoyt, 2000). In addition, one cytoplasmic dynein motorcontaining polypeptide, the dynein heavy chain (DHC), has also been implicated in mitotic spindle function (Hildebrandt and Hoyt, 2000). Using RNAi techniques, Goshima and Vale recently examined the mitotic functions of cytoplasmic dynein and all 25 fly kinesins in cultured Drosophila cells (Goshima and Vale, 2003). They found that four kinesins are needed for bipolar spindle assembly and four are crucial for metaphase chromosome alignment. Dynein plays a role in the metaphase-to-anaphase transition, and one kinesin is required for cytokinesis.Th...

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Functional Analysis of Human Microtubule-based Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA Interference

Zhu

Zhao

Bibikova

et al. 2005

MBoC

378

344

View full text Add to dashboard Cite

show abstract

“…Microtubule depolymerization, on the other hand, is stimulated by several members of the kinesin superfamily (Wordeman, 2005). In Drosophila, these include KLP10A, KLP59C (both kinesin-13 members; Rogers et al, 2004), and KLP67A (a kinesin-8; Goshima and Vale, 2003;Gandhi et al, 2004). KLP59C and KLP67A localize to centromeres/kinetochores during mitosis, suggesting that these kinesins could stimulate depolymerization of kinetochore microtubule plus ends (Rogers et al, 2004;Savoian et al, 2004;.…”

Section: Introductionmentioning

confidence: 99%

Poleward Tubulin Flux in Spindles: Regulation and Function in Mitotic Cells

Buster

Zhang

Sharp

2007

MBoC

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The poleward flux of tubulin subunits through spindle microtubules is a striking and conserved phenomenon whose function and molecular components remain poorly understood. To screen for novel components of the flux machinery, we utilized RNA interference to deplete regulators of microtubule dynamics, individually and in various combinations, from S2 cells and examined the resulting impact on flux rate. This led to the identification of two previously unknown flux inhibitors, KLP59C and KLP67A, and a flux promoter, Mini-spindles. Furthermore, we find that flux rate is regulated by functional antagonism among microtubule stabilizers and destabilizers specifically at plus ends. Finally, by examining mitosis on spindles in which flux has been up-or down-regulated or restored after the codepletion of antagonistic flux regulators, we show that flux is an integral contributor to anaphase A but is not responsible for chromosome congression, interkinetochore tension, or the establishment of normal spindle length during prometaphase/metaphase.

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“…During interphase fission yeast microtubule bundles, which are nucleated from MTOCs (microtubule organising centres) surrounding a centrally located nucleus, grow towards both cell ends to deposit factors that are required for the maintenance of cell polarity and to maintain the nucleus in the centre of the cell (Martin 2009;Chang and Nurse 1996;Tran et al 2000Tran et al , 2001. In the absence of the Klp5 or Klp6 motors some interphase Savoian et al (2004) Spindle length Gandhi et al (2004); Savoian and Glover (2010) Mitochondrial distribution Gandhi et al (2004) Central spindle stability and formation Gatt et al (2005) Spindle elongation Wang et al (2010) Homo sapiens KIF18A Chromosome congression Mayr et al (2007) Chromosome oscillation Stumpff et al (2008) West et al (2001) microtubules fail to pause at the cell end and continue to grow, resulting in long microtubules that bend around the cell cortex. This results in a defect in cell polarity particularly in elongated cells (West et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Role and regulation of kinesin-8 motors through the cell cycle

Millar

2014

Syst Synth Biol

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Members of the kinesin-8 motor family play a central role in controlling microtubule length throughout the eukaryotic cell cycle. Inactivation of kinesin-8 causes defects in cell polarity during interphase and astral and mitotic spindle length, metaphase chromosome alignment, timing of anaphase onset and accuracy of chromosome segregation. Although the biophysical mechanism by which kinesin-8 molecules influence microtubule dynamics has been studied extensively in a variety of species, a consensus view has yet to emerge. One reason for this might be that some members of the kinesin-8 family can associate to other microtubule-associated proteins, cell cycle regulatory proteins and other kinesin family members. In this review we consider how cell cycle specific modification and its association to other regulatory proteins may modulate the function of kinesin-8 to enable it to function as a master regulator of microtubule dynamics.

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TheDrosophilaKinesin-like Protein KLP67A Is Essential for Mitotic and Male Meiotic Spindle Assembly

Cited by 74 publications

References 54 publications

Functional Analysis of Human Microtubule-based Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA Interference

Functional Analysis of Human Microtubule-based Motor Proteins, the Kinesins and Dyneins, in Mitosis/Cytokinesis Using RNA Interference

Poleward Tubulin Flux in Spindles: Regulation and Function in Mitotic Cells

Role and regulation of kinesin-8 motors through the cell cycle

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