Divalent cations induce non-equilibrium phase transitions in tau-mediated microtubule bundles undergoing dynamic instability

Abstract

The microtubule-associated protein tau is known for its ability to alter microtubule (MT) dynamic instability in developing and mature neurons and for its role in the pathology of many neurodegenerative diseases. Bundling of Mts into small linear arrays (or fascicles) is a cardinal feature of the axon initial segment. While tau plays an important role in the structural stability of MT fascicles, the exact mechanism by which tau imparts MT bundle stabilization remains unclear. To help elucidate the nature of tau's role in physiological bundling of Mts, we have expanded on a recent platform for studying paclitaxel-free in vitro reaction mixtures of tubulin, GTP, and wild-type tau under dissipative, out-of-equilibrium conditions at 37 °C.