A unified model for microtubule rescue

Abstract

How microtubules transition from depolymerization to polymerization, known as rescue, is poorly understood. Here we examine two models for rescue: 1) an end-driven model in which the depolymerizing end stochastically switches to a stable state; and 2) a lattice-driven model in which rescue-sites are integrated into the microtubule prior to depolymerization. We test these models using a combination of computational simulations and in vitro experiments with purified tubulin. Our findings support the lattice-driven model by identifying repeated rescue sites in microtubules. In addition, we discover an important role for divalent cations in determining the frequency and location of rescue sites. We use wash-in experiments to show that divalent cations inhibit rescue during depolymerization, but not during the polymerization. We propose a unified model in which rescues are driven by embedded rescue sites in microtubules, but the activity of these sites is influenced by changes in the depolymerizing ends.