Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast
| Autor: | Eileen T. O'Toole, Adam Lamson, Christopher Edelmaier, Loren E. Hough, Ammon Crapo, Oliver Sweezy-Schindler, Zachary R. Gergely, J. Richard McIntosh, Matthew A. Glaser, Robert Blackwell, Meredith D. Betterton |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Fission Kinesins Nanotechnology Spindle Apparatus Biology Spindle pole body 03 medical and health sciences 0302 clinical medicine Microtubule mental disorders Schizosaccharomyces Mitosis Research Articles Multidisciplinary SciAdv r-articles Cell Biology biology.organism_classification Cell biology Spindle apparatus 030104 developmental biology Kinesin sense organs Schizosaccharomyces pombe Proteins Mitotic spindle assembly 030217 neurology & neurosurgery Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.1601603 |
| Popis: | A physical model that exhibits de novo bipolar spindle assembly is used to study the mechanisms of spindle bipolarity. Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition; this is the most fundamental construction problem that the spindle must solve. Microtubules, motors, and cross-linkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. We describe a physical model that exhibits de novo bipolar spindle formation. We began with physical properties of fission-yeast spindle pole body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive cross-linkers. Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self-assembly. By varying the features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive cross-linkers alone. We also identify characteristic failed states of spindle assembly—the persistent monopole, X spindle, separated asters, and short spindle, which are avoided by the creation and maintenance of antiparallel microtubule overlaps. Our model can guide the identification of new, multifaceted strategies to induce mitotic catastrophes; these would constitute novel strategies for cancer chemotherapy. |
| Databáze: | OpenAIRE |
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