Structural Evolution of Energy-Consuming Tau Mediated Microtubule Bundles

Abstract

Tau is an intrinsically disordered neuronal protein known to modulate microtubule dynamics through the suppression of dynamic instability. Recent studies have shown that Tau mediates dynamical linear microtubule bundles similar to microtubule fascicles observed in vivo, which are a cardinal feature of the axon initial segment (P. J. Chung, C. Song, et al. Nature Communications 2016, 7, 12278. DOI: 10.1038/ncomms12278 and ACS Macro Lett. 2018, 7, 228-232. DOI: 10.1021/acsmacrolett.7b00937). In order to better understand the architecture of these nanoscale energy-consuming dissipative structures, quantitative techniques of synchrotron small-angle x-ray scattering data—combined with TEM, and other analytical techniques—have been utilized. Here we show that under biologically relevant GTP and Mg2+ concentrations, microtubule bundles undergo a time induced transition, in which the wall to wall distance of the previously observed “pseudo-hexagonal” wide spacing dramatically drops, and remodels to form a tightly bound, “locked-hexagonal” structure, which in turn, induces a rapid depolymerization of the microtubule bundle. The structure and stability of these architectures appear to be Tau-isoform dependent and underscore the importance of the expression of distinct Tau-isoforms within neurons.