Measuring and modeling polymer gradients argues that spindle microtubules regulate their own nucleation

TL;DR

This study combines experiments and modeling to show that microtubule nucleators are activated upon binding to microtubules, which helps explain how spindle microtubule nucleation is spatially regulated during cell division.

Contribution

It provides evidence that microtubule nucleators are both localized and activated by microtubules, advancing understanding of spindle self-organization mechanisms.

Findings

Microtubule nucleators are only active when bound to microtubules.

Sharp decay in microtubule concentration at spindle interface.

Nucleator activity is enhanced upon microtubule binding.

Abstract

Spindles are self-organized microtubule-based structures that segregate chromosomes during cell division. The mass of the spindle is controlled by the balance between microtubule turnover and nucleation. The mechanisms that control the spatial regulation of microtubule nucleation remain poorly understood. Previous work has found that microtubule nucleators bind to microtubules in the spindle, but it is unclear if this binding regulates the activity of those nucleators. Here we use a combination of experiments and mathematical modeling to investigate this issue. We measure the concentration of tubulin and microtubules in and around the spindle. We found a very sharp decay in microtubules at the spindle interface, which is inconsistent with the activity of microtubule nucleators being independent of their association with microtubules and consistent with a model in which microtubule nucleators are only active when bound to a microtubule. This strongly argues that the activity of microtubule nucleators is greatly enhanced when bound to microtubules. Thus, microtubule nucleators are both localized and activated by the microtubules they generate.