Katanin Contributes to Interspecies Spindle Length Scaling in Xenopus

Loughlin, Rose; Wilbur, Jeremy D.; McNally, Francis J.; Nédélec, François; Heald, Rebecca

doi:10.1016/j.cell.2011.11.014

Cited by 186 publications

(282 citation statements)

References 41 publications

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“…Here we performed simulations with Cytosim software (Nedelec and Foethke, 2007). This cytoskeleton simulator is based on a Langevin dynamics approach and offers the possibility to take into account numerous components in minimal computational time due to a semi-implicit numerical integration scheme (Kozlowski et al, 2007;Loughlin et al, 2010Loughlin et al, , 2011Ward et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Letort¹,

Burute²

2017

Single Cell Biol

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The centrosome is positioned at the cell center by pushing and pulling forces transmitted by microtubules (MTs). Centrosome decentering is often considered to result from asymmetric, cortical pulling forces exerted in particular by molecular motors on MTs and controlled by external cues affecting the cell cortex locally. Here we used numerical simulations to investigate the possibility that it could equally result from the redistribution of pushing forces due to a reorientation of MTs. We first showed that MT gliding along cell edges and pivoting around the centrosome regulate MT rearrangement and thereby direct the spatial distribution of pushing forces, whereas the number, dynamics, and stiffness of MTs determine the magnitude of these forces. By modulating these parameters, we identified different regimes, involving both pushing and pulling forces, characterized by robust centrosome centering, robust off-centering, or "reactive" positioning. In the last-named conditions, weak asymmetric cues can induce a misbalance of pushing and pulling forces, resulting in an abrupt transition from a centered to an off-centered position. Taken together, these results point to the central role played by the configuration of the MTs on the distribution of pushing forces that position the centrosome. We suggest that asymmetric external cues should not be seen as direct driver of centrosome decentering and cell polarization but instead as inducers of an effective reorganization of the MT network, fostering centrosome motion to the cell periphery.

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Section: Resultsmentioning

confidence: 99%

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Letort¹,

Burute²

2017

Single Cell Biol

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“…Notably, proper regulation of astral microtubules is essential for mitotic spindle orientation in Drosophila neuroblasts (Siller and Doe, 2008). Although no evidence yet exists for a direct role of Kinesin-13 depolymerases in spindle orientation, the results discussed above suggest these microtubule enzymes, along with other related proteins (Loughlin et al, 2011), might serve an essential regulatory function at the interface between plus-ends and cortical spindle orientation complexes. Future studies using high resolution, real-time imaging to examine astral MT dynamics directly at the cortex during oriented cell division will be extremely valuable in understanding this process.…”

Section: Buttrick Et Al 2008mentioning

confidence: 97%

Molecular pathways regulating mitotic spindle orientation in animal cells

2013

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Orientation of the cell division axis is essential for the correct development and maintenance of tissue morphology, both for symmetric cell divisions and for the asymmetric distribution of fate determinants during, for example, stem cell divisions. Oriented cell division depends on the positioning of the mitotic spindle relative to an axis of polarity. Recent studies have illuminated an expanding list of spindle orientation regulators, and a molecular model for how cells couple cortical polarity with spindle positioning has begun to emerge. Here, we review both the wellestablished spindle orientation pathways and recently identified regulators, focusing on how communication between the cell cortex and the spindle is achieved, to provide a contemporary view of how positioning of the mitotic spindle occurs.Key words: Spindle, Microtubules, Oriented cell division, Polarity, Mitosis, Centrosome IntroductionAll multicellular animals are tasked with two fundamental developmental challenges: generating cellular diversity and forming three-dimensional tissues, both of which initiate from a singlecelled zygote. Cellular diversity is spawned by cell divisions yielding non-identical daughters, and tissue morphogenesis is established through the precise three-dimensional arrangement of cell divisions that form the overall architecture of the organism. Both of these essential challenges are resolved in part through oriented cell division, which regulates embryogenesis, organogenesis and cellular differentiation. Notably, oriented cell divisions, and hence asymmetric cell divisions, remain crucial throughout adulthood as well, functioning as the basis for tissue homeostasis during growth and wound repair. One primary feature of oriented cell division is the proper positioning of the mitotic spindle relative to a defined polarity axis. In principle, spindle orientation is achieved through signaling pathways that provide a molecular link between the cell cortex and spindle microtubules. These pathways are thought to elicit both static connections and dynamic forces on the spindle to achieve the desired orientation prior to cell division. Although our knowledge of the signaling molecules involved in this process and our understanding of how they each function at the molecular level remain limited, collective efforts over the years have shed light on the importance of spindle orientation to animal development and function. Moreover, emerging evidence shows an association between improper spindle orientation and a number of developmental diseases as well as tumor formation. The study of spindle orientation is therefore fundamental to both developmental biology and human disease.Over a century ago, Oscar Hertwig discovered that sea urchin embryos biased the orientation of the mitotic spindle along their long axis, which led to a model (the 'Hertwig Rule') in which cells orient divisions in response to mechanical forces (Hertwig, 1884). The Hertwig model stated that mechanical regulation was the primary determinant of spindle orien...

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“…The core message that arose from these studies was that anti-parallel overlapping microtubules were a convenient setting for polarity-sensitive motors to generate forces intrinsic to the spindle and, by the same mechanisms, that parallel microtubules would not promote relative motion but some degree of mechanical coupling. Thus, the mitotic spindle started to be regarded as a closed structure, with intrinsic properties dictating its own stability, symmetry, and scaling properties, paving the way for studies on spindle self-assembly in the following decades (Karsenti and Vernos 2001;Heald et al 1996;Loughlin et al 2011;Wuhr et al 2008).…”

Section: Basic Physical Principles Behind Mitotic Spindle Mechanicsmentioning

confidence: 99%

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

Pereira

Maiato

2012

Chromosome Res

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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.

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Katanin Contributes to Interspecies Spindle Length Scaling in Xenopus

Cited by 186 publications

References 41 publications

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Centrosome Centering and Decentering by Microtubule Network Rearrangement

Molecular pathways regulating mitotic spindle orientation in animal cells

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

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