Spatial Coordination of Spindle Assembly by Chromosome-Mediated Signaling Gradients

Caudron, Maïwen; Bunt, Gertrude; Bastiaens, Philippe I. H.; Karsenti, Eric

doi:10.1126/science.1115964

Cited by 287 publications

(303 citation statements)

References 24 publications

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“…2a, inset). Below this concentration threshold, nucleation events were almost non-existent, in agreement with results obtained previously 27 . Next, using Ran-NPs, we found that the complexes triggered microtubule nucleation and aster selforganization with a morphology and a timescale similar to those when assembled with uncoupled Ran (Fig.…”

Section: Magnetic Nanoparticles Controlling Microtubule Assemblysupporting

confidence: 92%

“…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%

“…To test this hypothesis, we adapted a reaction-diffusion model originally used to describe how RanGTP gradients, stimulated by RCC1 bound to chromatin, may influence meiotic spindle formation 27 . The model consists of computing the concentration in space of different biochemical species, including RanGTP, importins and MAPs, using the kinetic properties of the signalling pathways and the protein diffusion characteristics (Supplementary Section S5).…”

Section: Reaction-diffusion Influences Microtubule Assemblymentioning

confidence: 99%

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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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Section: Magnetic Nanoparticles Controlling Microtubule Assemblysupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Reaction-diffusion Influences Microtubule Assemblymentioning

confidence: 99%

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Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

et al. 2013

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“…The development of imaging techniques allowed direct experimental observation of activity gradients in the control of the mitotic spindle [6,8]. This process involves the diffusible small GTPase Ran.…”

Section: Spatial Gradients In Single-protein Modules Activity Gradienmentioning

confidence: 99%

“…For instance, fluorescence resonance energy transfer-based biosensors enabled the detection of gradients of the small GTPases Cdc42 [5] and Ran [6][7][8] as well as of phosphorylated stathmin, a microtubule-binding protein [9]. With suitable probes, even highly unstable enzyme-substrate complexes can nowadays be monitored with sub-cellular spatial resolution [10].…”

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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The Role of the RanGTPase in Mitotic Spindle Assembly

Renshaw

Wilde

2011

Encyclopedia of Life Sciences

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Mitosis is the process whereby a cell separates its paired chromosomes into two new identical daughter cells. To achieve this and maintain the correct amount of deoxyribo nuclic acid (DNA) in the cells, the cell forms a framework called the mitotic spindle onto which the chromosomes attach and then get pulled into the new daughter cells. The mitotic spindle is made up of microtubules and associated proteins. The GTPase Ran, which is important for nuclear import and export, plays important roles in regulating the formation of the mitotic spindle. Ran can bind and hydrolyse guanosine triphosphate (GTP), which enables it to regulate several cellular processes. Generation of Ran‐GTP at the chromosomes creates an intracellular gradient that provides directionality to nuclear cytoplasmic transport during interphase and creates an environment around the chromosomes to facilitate spindle assembly. Key Concepts: Ran is a small GTPase. During interphase, spindle assembly factors bind to Importin‐β and are transported into the nucleus. Ran‐GTP is generated at chromosomes and releases spindle assembly factors from inhibitory binding to Importin‐β. Gradients of Ran‐GTP and released cargo proteins are generated in mitotic cells that are important for regulating many activities.

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Spatial Coordination of Spindle Assembly by Chromosome-Mediated Signaling Gradients

Cited by 287 publications

References 24 publications

Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles

Signaling cascades as cellular devices for spatial computations

The Role of the RanGTPase in Mitotic Spindle Assembly

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