A unified model for microtubule rescue

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.