Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux

Ma, Nan; Tulu, U. Serdar; Ferenz, Nick P.; Fagerstrom, Carey J.; Wilde, Andrew; Wadsworth, Patricia

doi:10.1091/mbc.e09-07-0601

Cited by 82 publications

(93 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human U2OS 14 11 0.5 SL-13.3 (Ganem et al 2005) and 15.4 (Arnaoutov et al 2005); MD-12 (Arnaoutov et al 2005) and 9.4 (Tedeschi et al 2007);and F-0.53 (Ganem et al 2005) and 0.53 (Maffini et al 2009) (Ma et al 2010); MD-13 (our unpublished observations); and F-1.37 (Ferenz and Wadsworth 2007) and 0.96 (Ma et al 2010) 1.7…”

Section: A Relation Between Flux Velocity Spindle Size and Metaphasementioning

confidence: 59%

Maturation of the kinetochore-microtubule interface and the meaning of metaphase

Pereira

Maiato

2012

Chromosome Res

View full text Add to dashboard Cite

Chromosome positioning at the equator of the mitotic spindle emerges out of a relatively entropic background. At this moment, termed metaphase, all kinetochores have typically captured microtubules leading to satisfaction of the spindle-assembly checkpoint, but the cell does not enter anaphase immediately. The waiting time in metaphase is related to the kinetics of securin and cyclin B1 degradation, which trigger sisterchromatid separation and promote anaphase processivity, respectively. Yet, as judged by metaphase duration, such kinetics vary widely between cell types and organisms, with no evident correlation to ploidy or cell size. During metaphase, many animal and plant spindles are also characterized by a conspicuous "flux" activity characterized by continuous poleward translocation of spindle microtubules, which maintain steady-state length and position. Whether spindle microtubule flux plays a specific role during metaphase remains arguable. Based on known experimental parameters, we have performed a comparative analysis amongst different cell types from different organisms and show that spindle length, metaphase duration and flux velocity combine within each system to obey a quasi-universal rule. As so, knowledge of two of these parameters is enough to estimate the third. This trend indicates that metaphase duration is tuned to allow approximately one kinetochore-to-pole round of microtubule flux. We propose that the time cells spend in metaphase evolved as a quality enhancement step that allows for the uniform stabilization/correction of kinetochore-microtubule attachments, thereby promoting mitotic fidelity.

show abstract

Section: A Relation Between Flux Velocity Spindle Size and Metaphasementioning

confidence: 59%

Maturation of the kinetochore-microtubule interface and the meaning of metaphase

Pereira

Maiato

2012

Chromosome Res

View full text Add to dashboard Cite

show abstract

“…However, the interaction of TPX2 with microtubules in cells is dynamic, as evidenced by its poleward motion in the spindle (9). One possibility that can account for these differences is that modifications, such as phosphorylation, or interactions with other binding partners, such as dynein, regulate TPX2 dynamic behavior in cells.…”

Section: Discussionmentioning

confidence: 99%

“…During spindle formation, TPX2 is required for microtubule formation near kinetochores, an activity that requires GTP-bound Ran, which relieves the inhibitory action of importin ␣/␤ on TPX2 (8). In addition, it has been demonstrated that the C terminus of TPX2 binds to the bipolar kinesin Eg5 and targets the motor to spindle microtubules (9,10). Expression of TPX2 lacking the C-terminal 35 amino acids, which contribute to Eg5 binding, results in defective spindles with greatly reduced Eg5 on spindle microtubules, unfocussed spindle poles, and bent and buckled microtubules (11).…”

mentioning

confidence: 99%

TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule

Balchand

Mann

Titus

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: TPX2 is a mitotic microtubule-associated protein that regulates the kinesin, Eg5. Results: Full-length TPX2 is a more potent inhibitor of Eg5 velocity than truncated TPX2; differential regulation by TPX2 was not observed for monomeric Eg5. Conclusion: TPX2 inhibits Eg5 as a roadblock and by direct interaction with Eg5. Significance: TPX2 may contribute to the spatial and temporal regulation of the mitotic motor Eg5.

show abstract

“…Tpx2 interacts with several molecules, including the kinase Aurora A (6-8), the microtubule-sliding kinesin Eg5 (25,26), and the plus-end directed kinesin Hklp2/Kif15 (2, 27). We therefore analyzed the status of these proteins in Tpx2-depleted cells.…”

Section: Tpx2 Is Essential For Chromatin-dependent Microtubule Nucleamentioning

confidence: 99%

Tpx2 Controls Spindle Integrity, Genome Stability, and Tumor Development

et al. 2012

View full text Add to dashboard Cite

Tpx2 is a microtubule-associated protein that activates the cell-cycle kinase Aurora A and regulates the mitotic spindle. Overexpression of Tpx2 is associated with the development of different human tumors and strongly correlates with chromosomal instability. By analyzing a conditional null mutation in the mouse Tpx2 gene, we show here that Tpx2 expression is essential for spindle function and chromosome segregation in the mouse embryo. Conditional genetic ablation of Tpx2 in primary cultures resulted in deficient microtubule nucleation from DNA and aberrant spindles during prometaphase. These cells eventually exited from mitosis without chromosome segregation. In addition, Tpx2 haploinsufficiency led to the accumulation of aneuploidies in vivo and increased susceptibility to spontaneous lymphomas and lung tumors. Together, our findings indicate that Tpx2 is essential for maintaining genomic stability through its role in spindle regulation. Subtle changes in Tpx2 expression may favor tumor development in vivo. Cancer Res; 72(6); 1518-28. Ó2012 AACR.

show abstract

Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux

Cited by 82 publications

References 47 publications

Maturation of the kinetochore-microtubule interface and the meaning of metaphase

Maturation of the kinetochore-microtubule interface and the meaning of metaphase

TPX2 Inhibits Eg5 by Interactions with Both Motor and Microtubule

Tpx2 Controls Spindle Integrity, Genome Stability, and Tumor Development

Contact Info

Product

Resources

About