Biology subjects

Decker, F.

Publications and source records attributed to Decker, F..

5 recordsLinked to original sources

bioRxiv2021

A gelation transition enables the self-organization of bipolar metaphase spindles

The mitotic spindle is a highly dynamic bipolar structure that emerges from the self-organization of microtubules, molecular motors, and other proteins. Sustained motor-driven poleward flows of short dynamic microtubules play a key role in the bipolar organization of spindles. However, it is not understood how the local activity of motor proteins generates these large-scale coherent poleward flows. Here, we combine experiments and simulations to show that a gelation transition enables long-ranged microtubule transport causing spindles to self-organize into two oppositely polarized microtubule gels. Laser ablation experiments reveal that local active stresses generated at the spindle midplane propagate through the structure thereby driving global coherent microtubule flows. Simulations show that microtubule gels undergoing rapid turnover can exhibit long stress relaxation times, in agreement with the long-ranged flows observed in experiments. Finally, we show that either disrupting such flows or decreasing the network connectivity can lead to a microtubule polarity reversal in spindles both in the simulations and in the experiments. Thus, we uncover an unexpected connection between spindle rheology and architecture in spindle self-organization.

biophysics↗

bioRxiv2020

Spatial Variation of Microtubule Depolymerization in Large Asters Suggests Regulation by MAP Depletion

Microtubule plus end depolymerization rate is a potentially important target of physiological regulation, but it has been challenging to measure, so its role in spatial organization is poorly understood. Here we apply a method for tracking plus ends based on time difference imaging to measure depolymerization rates in large interphase asters growing in Xenopus egg extract. We observed strong spatial regulation of depolymerization rates, which were almost two-fold higher in the aster interior compared to the periphery, and much less regulation of polymerization or catastrophe rates. We interpret these data in terms of a limiting component model, where aster growth results in lower levels of soluble tubulin and MAPs in the interior cytosol compared to that at the periphery. The steady-state polymer fraction of tubulin was ∼30%, so tubulin is not strongly depleted in the aster interior. We propose that the limiting component for microtubule assembly is a MAP that inhibits depolymerization, and that egg asters are tuned to low microtubule density.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2020

Spindle scaling is governed by cell boundary regulation of microtubule nucleation

Cellular organelles such as the mitotic spindle adjust their size to the dimensions of the cell. It is widely understood that spindle scaling is governed by regulation of microtubule polymerization. Here we use quantitative microscopy in living zebrafish embryos and Xenopus egg extracts in combination with theory to show that microtubule polymerization dynamics are insufficient to scale spindles and only contribute below a critical cell size. In contrast, microtubule nucleation governs spindle scaling for all cell sizes. We show that this hierarchical regulation arises from the partitioning of a nucleation inhibitor to the cell membrane. Our results reveal that cells differentially regulate microtubule number and length using distinct geometric cues to maintain a functional spindle architecture over a large range of cell sizes.

cell biology↗

bioRxiv2017

A size-invariant bud-length timer enables robustness in yeast cell size control

Cell populations across nearly all forms of life generally maintain a characteristic cell type-dependent size, but how size control is achieved has been a long-standing question. Prior work has uncovered diverse size control strategies operating at distinct cell cycle stages, but it is unclear how these numerous pathways are integrated to provide robust, systems-level cell size control for any organism. Here, we probe cell growth and size control in budding yeast that can be reversibly blocked from bud initiation. While blocked, cells continue to grow isotropically, increasing their volume by more than an order of magnitude over unperturbed cells. Upon release, these giant yeast resume budding and the population returns to its initial volume distribution within a few cell division cycles. Size control under these conditions does not require an explicit molecular size sensor. Instead, our observations are consistent with a size-invariant bud growth timer specifying the duration of S/G2/M to limit daughter cell size.

cell biology↗

bioRxiv2017

Autocatalytic microtubule nucleation determines the size and mass of spindles

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation (1, 2). Previous evidence suggests that microtubules nucleate throughout the spindle structure (3-5). However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. Thus, the size of spindles is determined by the distance where one microtubule nucleates on average less than one new microtubule. This mechanism provides an upper limit to spindle size even when resources are not limiting and may have implications for spindle scaling during development (6, 7).

biophysics↗