The effect of multivalent cations and Tau on paclitaxel-stabilized microtubule assembly, disassembly, and structure

Abstract

In this review we describe recent studies directed at understanding the formation of novel nanoscale assemblies in biological materials systems. In particular, we focus on the effects of multivalent cations, and separately, of microtubule-associated protein (MAP) Tau, on microtubule (MT) ordering (bundling), MT disassembly, and MT structure. Counter-ion directed bundling of paclitaxel-stabilized MTs is a model electrostatic system, which parallels efforts to understand MT bundling by intrinsically disordered proteins (typically biological polyampholytes) expressed in neurons. We describe studies, which reveal an unexpected transition from tightly spaced MT bundles to loose bundles consisting of strings of MTs as the valence of the cationic counter-ion decreases from Z = 3 to Z = 2. This transition is not predicted by any current theories of polyelectrolytes. Notably, studies of a larger series of divalent counter-ions reveal strong ion specific effects. Divalent counter-ions may either bundle or depolymerize paclitaxel-stabilized MTs. The ion concentration required for depolymerization decreases with increasing atomic number. In a more biologically related system we review synchrotron small angle x-ray scattering (SAXS) studies on the effect of the Tau on the structure of paclitaxel-stabilized MTs. The electrostatic binding of MAP Tau isoforms leads to an increase in the average radius of microtubules with increasing Tau coverage (i.e. a re-distribution of protofilament numbers in MTs). Finally, inspired by MTs as model nanotubes, we briefly describe other more robust lipid-based cylindrical nanostructures, which may have technological applications, for example, in drug encapsulation and delivery.

Reversible Control of Spacing in Charged Lamellar Membrane Hydrogels by Hydrophobically Mediated Tethering with Symmetric and Asymmetric Double-End-Anchored Poly(ethylene glycol)s

“…61 Acylation of mPEG-NH 2 ( 1a,b ) with the lipid building block DOB (3,4-dioleyloxybenzoic acid) 48,49 yielded the control single-end-anchored PEG-lipids ( 3a,b ; L-PEG) on a gram scale. Monofunctionalization of amine-terminated PEG ( 2a,b ) with DOB to yield 5a,b requires a less reactive acylation reagent and low temperature 49,50 and yields the symmetric double-end-anchored PEG ( 4a,b ; L-PEG-L) as a side product. The monofunctionalized PEG ( 5a,b ) was separated by chromatography and acylated with oleic acid to yield the asymmetric double-end-anchored PEGs ( 6a,b ; L-PEG-L’).…”

<p>Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson’s Disease</p>

“…Consistent with previous studies, Tau is thought to stabilize axonal microtubules and Tau phosphorylation leads to microtubule depolymerization. 29 The motor dysfunction was observed in animal models and PD patients. 2 Here, behavioral tests were used to evaluate the motor function of the mice in each group including rotarod test, static rod test and pole test.…”

Effect of Divalent Cations on the Structure and Mechanics of Vimentin Intermediate Filaments

“…Interestingly, divalent cation species appear to exhibit increasing effectiveness at promoting VIF aggregation according to their atomic number (14). Studies of other proteins have shown that ion-protein interactions can strongly depend on the ion species even when valency is unchanged (14,(16)(17)(18)(19)(20); this is often referred to as the Hofmeister effect. Corresponding species-specific interactions have not been widely explored in VIF networks.…”