title: Self-organization of anastral spindles by synergy of dynamic instability, autocatalytic microtubule production, and a spatial signaling gradient.
abstract: Assembly of the mitotic spindle is a classic example of macromolecular self-organization. During spindle assembly, microtubules (MTs) accumulate around chromatin. In centrosomal spindles, centrosomes at the spindle poles are the dominating source of MT production. However, many systems assemble anastral spindles, i.e., spindles without centrosomes at the poles. How anastral spindles produce and maintain a high concentration of MTs in the absence of centrosome-catalyzed MT production is unknown. With a combined biochemistry-computer simulation approach, we show that the concerted activity of three components can efficiently concentrate microtubules (MTs) at chromatin: (1) an external stimulus in form of a RanGTP gradient centered on chromatin, (2) a feed-back loop where MTs induce production of new MTs, and (3) continuous re-organization of MT structures by dynamic instability. The mechanism proposed here can generate and maintain a dissipative MT super-structure within a RanGTP gradient.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Clausen
authors.forename: Katharina
authors.initials: K
authors.lastname: Ribbeck
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002384:Catalysis; D002474:Cell-Free System; D002843:Chromatin / Q000378:metabolism; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D005260:Female; D006160:Guanosine Triphosphate / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis; D020125:Mutation, Missense; D009865:Oocytes; D017239:Paclitaxel / Q000494:pharmacology; D017510:Protein Folding; D008941:Spindle Apparatus / Q000502:physiology*; D013269:Stochastic Processes; D014404:Tubulin / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000494:pharmacology*
chemical_list: D002843:Chromatin; D014404:Tubulin; D029867:Xenopus Proteins; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein; D017239:Paclitaxel