Gradients in the self-organization of the mitotic spindle

Bastiaens, Philippe I. H.; Caudron, Maïwen; Niethammer, Philipp; Karsenti, Eric

doi:10.1016/j.tcb.2006.01.005

Cited by 109 publications

(93 citation statements)

References 64 publications

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“…The defects in spindle organization we find are consistent with this effect because we see a significant increase in short MTs near poles, which is likely due to stabilization of the plus ends of spindle MTs that grow toward the spindle equator. This type of biased MT growth toward the chromosomes has been demonstrated in studies tracking GFP-EB1 in the spindle (Piehl and Cassimeris, 2003) and may be due to stabilization of MTs near chromosomes based on the Ran-GTP gradient (Wollman et al, 2005;Bastiaens et al, 2006;Kalab et al, 2006;O'Connell and Khodjakov, 2007;Kalab and Heald, 2008). Alternatively, the increase in MTs near the poles could be a result of an increase in nucleation of MTs from the centrosome as paclitaxel has been shown to affect the MT nucleation rate (Schiff and Horwitz, 1981).…”

Section: What Is the Relationship Between Spindle Mt Dynamics And Orgmentioning

confidence: 85%

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

Rizk

Bohannon

Wetzel

et al. 2009

MBoC

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Within the mitotic spindle, there are multiple populations of microtubules with different turnover dynamics, but how these different dynamics are maintained is not fully understood. MCAK is a member of the kinesin-13 family of microtubule-destabilizing enzymes that is required for proper establishment and maintenance of the spindle. Using quantitative immunofluorescence and fluorescence recovery after photobleaching, we compared the differences in spindle organization caused by global suppression of microtubule dynamics, by treating cells with low levels of paclitaxel, versus specific perturbation of spindle microtubule subsets by MCAK inhibition. Paclitaxel treatment caused a disruption in spindle microtubule organization marked by a significant increase in microtubules near the poles and a reduction in K-fiber fluorescence intensity. This was correlated with a faster t 1/2 of both spindle and K-fiber microtubules. In contrast, MCAK inhibition caused a dramatic reorganization of spindle microtubules with a significant increase in astral microtubules and reduction in K-fiber fluorescence intensity, which correlated with a slower t 1/2 of K-fibers but no change in the t 1/2 of spindle microtubules. Our data support the model that MCAK perturbs spindle organization by acting preferentially on a subset of microtubules, and they support the overall hypothesis that microtubule dynamics is differentially regulated in the spindle. INTRODUCTIONThe cytoskeleton must undergo dramatic reorganization as cells transition from interphase to mitosis to assemble the mitotic spindle. The spindle is a macromolecular structure composed of a dynamic array of microtubules (MTs) and their associated proteins that is necessary for proper chromosome segregation (Compton, 2000;Walczak and Heald, 2008). At the onset of mitosis, there is an increase in MT turnover that allows for breakdown of the interphase array and assembly of the mitotic spindle (Saxton et al., 1984;. This change is correlated with an increased catastrophe frequency (transition from growth to shrinkage) and a decreased rescue frequency (transition from shrinkage to growth) (Belmont et al., 1990;Gliksman et al., 1992;Verde et al., 1992;Rusan et al., 2001). The changes in MT dynamics are also correlated with a change in MT polymer levels during mitosis (Zhai et al., 1996). At nuclear envelope breakdown, there is a dramatic decrease in MT polymer levels, which may allow the cell to rapidly assemble a mitotic spindle because the released tubulin dimers can polymerize into new spindle MTs. As the cell progresses from mitosis to the next interphase, there is no change in the levels of MT polymer (Zhai et al., 1996), suggesting that MT polymer gets reorganized to reform the interphase MT cytoskeleton, without a significant change in the dynamics of the MTs. These studies highlight the need for the cell to possess a mechanism to temporally regulate MT dynamics.In addition to the temporal changes in dynamics throughout the cell cycle, the dynamics of MTs within mitosis are also...

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Section: What Is the Relationship Between Spindle Mt Dynamics And Orgmentioning

confidence: 85%

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

Rizk

Bohannon

Wetzel

et al. 2009

MBoC

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“…Remarkable studies have enabled the discovery of intracellular gradients of RanGTP, stimulated by RCC1 and emanating from chromosomes, which can be described as a reaction-diffusion process that supports the spindle machinery in cell division 27,29,[35][36][37] . Interestingly, by manipulating RanQ69L-GTP and RCC1 signalling grafted to magnetic nanoparticles, we have demonstrated experimentally how cascading reaction-diffusion signals may directly influence the position of asymmetric microtubule arrays.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

et al. 2013

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Decisions on the fate of cells and their functions are dictated by the spatiotemporal dynamics of molecular signalling networks. However, techniques to examine the dynamics of these intracellular processes remain limited. Here, we show that magnetic nanoparticles conjugated with key regulatory proteins can artificially control, in time and space, the Ran/RCC1 signalling pathway that regulates the cell cytoskeleton. In the presence of a magnetic field, RanGTP proteins conjugated to superparamagnetic nanoparticles can induce microtubule fibres to assemble into asymmetric arrays of polarized fibres in Xenopus laevis egg extracts. The orientation of the fibres is dictated by the direction of the magnetic force. When we locally concentrated nanoparticles conjugated with the upstream guanine nucleotide exchange factor RCC1, the assembly of microtubule fibres could be induced over a greater range of distances than RanGTP particles. The method shows how bioactive nanoparticles can be used to engineer signalling networks and spatial self-organization inside a cell environment.

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“…The phosphorylated protein (c) diffuses into the cell and gets dephosphorylated by the phosphatase at rate v I . The spatiotemporal dynamics of the phosphorylated protein form c and of the unphosphorylated form c I of the interconvertible protein are governed by the following reaction-diffusion equations, (10) The boundary conditions are the following, (11) In contrast to the previous section, here we allow for any functional form of the phosphatase rate v I . In this general case, the following can be derived.…”

Section: Emergence Of Spatial Gradients Of Protein Abundances Within mentioning

confidence: 99%

“…With suitable probes, even highly unstable enzyme-substrate complexes can nowadays be monitored with sub-cellular spatial resolution [10]. These studies have revealed that spatial gradients of signaling molecules play important roles in the spatial coordination of cell division processes, which often employ small GTPases to generate spatial 'clues' [11].…”

Section: Introductionmentioning

confidence: 99%

Signaling cascades as cellular devices for spatial computations

Stelling

Kholodenko

2008

J. Math. Biol.

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Signaling networks usually include protein-modification cycles. Cascades of such cycles are the backbones of multiple signaling pathways. Protein gradients emerge from the spatial separation of opposing enzymes, such as kinases and phosphatases, or guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) for GTPase cycles. We show that different diffusivities of an active protein form and an inactive form leads to spatial gradients of protein abundance in the cytoplasm. For a cascade of cycles, using a discrete approximation of the space, we derive an analytical expression for the spatial gradients and show that it converges to an exact solution with decreasing the size of the quantization. Our results facilitate quantitative analysis of the dependence of spatial gradients on the network topology and reaction kinetics. We demonstrate how different cascade designs filter and process the input information to generate precise, complex spatial guidance for multiple GTPase effector processes. Thus, protein-modification cascades may serve as devices to compute complex spatial distributions of target proteins within intracellular space.

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Gradients in the self-organization of the mitotic spindle

Cited by 109 publications

References 64 publications

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

MCAK and Paclitaxel Have Differential Effects on Spindle Microtubule Organization and Dynamics

Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

Signaling cascades as cellular devices for spatial computations

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