Regulation of Microtubule Dynamics by Reaction Cascades Around Chromosomes

• Published in: Science (American Association for the Advancement of Science) Vol. 322; no. 5905; pp. 1243 - 1247
• Main Authors: Athale, Chaitanya A, Dinarina, Ana, Mora-Coral, Maria, Pugieux, Céline, Nedelec, Francois, Karsenti, Eric
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 21.11.2008; The American Association for the Advancement of Science
• Subjects: Animals; Anura; Asymmetry; Biological and medical sciences; Cell Cycle Proteins - physiology; Cell cycle, cell proliferation; Cell physiology; Cellular biology; Centrosome - physiology; Centrosomes; Chromatin; Chromatin - physiology; Chromosomes; Chromosomes, Human - physiology; Computer Simulation; Diffusion; DNA; Eggs; Frogs; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Humans; Microtubule-Associated Proteins - physiology; Microtubules; Microtubules - physiology; Modeling; Models, Biological; Molecular and cellular biology; Nuclear Proteins - physiology; Ovum - cytology; Phosphoproteins - physiology; Positive feedback; ran GTP-Binding Protein - metabolism; Spindle Apparatus - physiology; Xenopus; Xenopus Proteins - physiology; Gradient; Regulation(control); Dynamics; Stabilization; Chromosome; Microtubule; Mitotic spindle; Cell signaling
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1161820

During spindle assembly, chromosomes generate gradients of microtubule stabilization through a reaction-diffusion process, but how this is achieved is not well understood. We measured the spatial distribution of microtubule aster asymmetry around chromosomes by incubating centrosomes and micropatterned chromatin patches in frog egg extracts. We then screened for microtubule stabilization gradient shapes that would generate such spatial distributions with the use of computer simulations. Only a long-range, sharply decaying microtubule stabilization gradient could generate aster asymmetries fitting the experimental data. We propose a reaction-diffusion model that combines the chromosome generated Ran-guanosine triphosphate-Importin reaction network to a secondary phosphorylation network as a potential mechanism for the generation of such gradients.