Minireview - Microtubules and Tubulin Oligomers: Shape Transitions and Assembly by Intrinsically Disordered Protein Tau and Cationic Biomolecules

Abstract

In this minireview, which is part of a special issue in honor of Jacob N. Israelachvili's remarkable research career on intermolecular forces and interfacial science, we present studies of structures, phase behavior, and forces in reaction mixtures of microtubules (MTs) and tubulin oligomers with either intrinsically disordered protein (IDP) Tau, cationic vesicles, or the polyamine spermine (4+). Bare MTs consist of 13 protofilaments (PFs), on average, where each PF is made of a linear stack of αβ-tubulin dimers (i.e., tubulin oligomers). We begin with a series of experiments which demonstrate the flexibility of PFs toward shape changes in response to local environmental cues. First, studies show that MT-associated protein (MAP) Tau controls the diameter of microtubules upon binding to the outer surface, implying a shape change in the cross-sectional area of PFs forming the MT perimeter. The diameter of a MT may also be controlled by the charge density of a lipid bilayer membrane that coats the outer surface. We further describe an experimental study where it is unexpectedly found that the biologically relevant polyamine spermine (+4e) is able to depolymerize taxol-stabilized microtubules with efficiency that increases with decreasing temperature. This MT destabilization drives a dynamical structural transition where inside-out curving of PFs, during the depolymerization peeling process, is followed by reassembly of ring-like curved PF building blocks into an array of helical inverted tubulin tubules. We finally turn to a very recent study on pressure−distance measurements in bundles of MTs employing the small-angle X-ray scattering (SAXS)-osmotic pressure technique, which complements the surface-forces-apparatus technique developed by Jacob N. Israelachvili. These latter studies are among the very few which are beginning to shed light on the precise nature of the interactions between MTs mediated by MAP Tau in 37 °C reaction mixtures containing GTP and lacking taxol.

Hierarchical Assembly Pathways of Spermine-Induced Tubulin Conical-Spiral Architectures

“…Tetravalent spermine effectively promotes tubulin assembly into helical and double-helical structures and bundle formation, − most likely by forming ion bridges between dimers. , Here we show the effect of spermine, at millimolar concentrations, on tubulin assembly. We discovered multiple hierarchical architectures and followed the transitions between them in real time.…”

Triggering Cation-Induced Contraction of Cytoskeleton Networks via Microfluidics

“…However, due to the polyelectrolyte nature of both actin and microtubules, changes to the ionic conditions of the network environment can also trigger rearrangements in actin and microtubule networks. For example, high concentrations of Mg 2+ ions have been shown to induce bundling and crosslinking of actin filaments [20][21][22][23] and microtubules [24,25] via counterion crossbridges. Increasing Mg 2+ concentration has also been shown to promote higher order structure formation in both actin and microtubule networks in vitro and in vivo [26][27][28][29][30][31].…”