Dynamical decoration of stabilized-microtubules by Tau-proteins

Jordan Hervy,Dominique J Bicout

doi:10.1038/s41598-019-48790-1

Abstract

Tau is a microtubule-associated protein that regulates axonal transport, stabilizes and spatially organizes microtubules in parallel networks. The Tau-microtubule pair is crucial for maintaining the architecture and integrity of axons. Therefore, it is essential to understand how these two entities interact to ensure and modulate the normal axonal functions. Based on evidence from several published experiments, we have developed a two-dimensional model that describes the interaction between a population of Tau proteins and a stabilized microtubule at the scale of the tubulin dimers (binding sites) as an adsorption-desorption dynamical process in which Tau can bind on the microtubule outer surface via two distinct modes: a longitudinal (along a protofilament) and lateral (across adjacent protofilaments) modes. Such a process yields a dynamical distribution of Tau molecules on the microtubule surface referred to as microtubule decoration that we have characterized at the equilibrium using two observables: the total microtubule surface coverage with Tau’s and the distribution of nearest neighbors Tau’s. Using both analytical and numerical approaches, we have derived expressions and computed these observables as a function of key parameters controlling the binding reaction: the stoichiometries of the Taus in the two binding modes, the associated dissociation constants and the ratio of the Tau concentration to that of microtubule tubulin dimers.

Highlights

Tau-MT binding sites: The exact Tau-MT binding sites are still not well defined[29]
The decoration of microtubules with Taus is described at the equilibrium by the system of coupled non-linear equations in Eq (2) with insertion probabilities of Taus given in Eq (3)
Our main motivation in developing this work has been the paramount importance of the interactions between Tau proteins and microtubules in axons

Summary

Introduction

Tau-MT binding sites: The exact Tau-MT binding sites are still not well defined[29]. Comparisons between Tau decorated and control microtubules using cryo-electron microscopy revealed that binding of Tau proteins occurs on the outer surface of microtubules[30,31,32]; an evidence supported using atomic force microscopy[33]. A study in 2003 reported a possible binding site on the inner surface of microtubules close to the taxol-binding site on β-tubulin[34]. A recent high resolution cryo-EM study has shown that in both experimental conditions, Tau was always bound on the outer surface of microtubules[32].

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Conclusion