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

Journal Article · · Langmuir

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. Furthermore, 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.

Research Organization:
Univ. of California, Santa Barbara, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
FG02-06ER46314
OSTI ID:
1763429
Journal Information:
Langmuir, Vol. 35, Issue 48; ISSN 0743-7463
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English

References (42)

Gel-expanded to gel-condensed transition in neurofilament networks revealed by direct force measurements journal November 2009
Selective stabilization of tau in axons and microtubule-associated protein 2C in cell bodies and dendrites contributes to polarized localization of cytoskeletal proteins in mature neurons. journal February 1996
How Shape Affects Microtubule and Nanoparticle Assembly journal February 2014
Neurofilament networks: Salt-responsive hydrogels with sidearm-dependent phase behavior journal July 2016
Microtubule Protofilament Number Is Modulated in a Stepwise Fashion by the Charge Density of an Enveloping Layer journal January 2007
Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains. journal April 1989
MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: an immunocytochemical study of cultured rat cerebrum journal October 1987
Comparison between 102k and 20k Poly(ethylene oxide) Depletants in Osmotic Pressure Measurements of Interfilament Forces in Cytoskeletal Systems journal January 2018
Interplay between Liquid Crystalline and Isotropic Gels in Self-Assembled Neurofilament Networks journal July 2008
MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction journal August 2002
Transformation of taxol-stabilized microtubules into inverted tubulin tubules triggered by a tubulin conformation switch journal January 2014
The MAP2/Tau family of microtubule-associated proteins journal December 2004
The Orderly Chaos of Proteins journal April 2011
Microtubules as a target for anticancer drugs journal April 2004
Intrinsically unstructured proteins journal October 2002
Dynamic instability of microtubule growth journal November 1984
Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment journal July 2016
From The Cover: Higher-order assembly of microtubules by counterions: From hexagonal bundles to living necklaces journal November 2004
Tau protein binds to microtubules through a flexible array of distributed weak sites journal November 1991
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17 journal June 1998
The primary structure and heterogeneity of tau protein from mouse brain journal January 1988
Taxol Allosterically Alters the Dynamics of the Tubulin Dimer and Increases the Flexibility of Microtubules journal October 2008
Human Microtubule-Associated-Protein Tau Regulates the Number of Protofilaments in Microtubules: A Synchrotron X-Ray Scattering Study journal July 2009
Intrinsically unstructured proteins and their functions journal March 2005
Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. journal June 1986
MAP2 is a component of crossbridges between microtubules and neurofilaments in the neuronal cytoskeleton: quick-freeze, deep-etch immunoelectron microscopy and reconstitution studies journal August 1988
Refined structure of αβ-tubulin at 3.5 Å resolution 1 1Edited by I. A. Wilson journal November 2001
Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons journal February 1990
The axon initial segment and the maintenance of neuronal polarity journal July 2010
Structure, Assembly, and Disassembly of Tubulin Single Rings journal September 2018
Measurement of the repulsive force between polyelectrolyte molecules in ionic solution: hydration forces between parallel DNA double helices. journal May 1984
Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules journal November 2015
Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury journal July 2009
The microtubule binding domain of tau protein journal June 1989
Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau journal March 1994
Structure of tubulin at 6.5 Å and location of the taxol-binding site journal June 1995
Neurofilament sidearms modulate parallel and crossed-filament orientations inducing nematic to isotropic and re-entrant birefringent hydrogels journal July 2013
Cationic liposome-microtubule complexes: Pathways to the formation of two-state lipid-protein nanotubes with open or closed ends journal July 2005
Microtubule Polymerization Dynamics journal November 1997
Cross-linker system between neurofilaments, microtubules and membranous organelles in frog axons revealed by the quick-freeze, deep-etching method journal July 1982
A central role for polyamines in microtubule assembly in cells journal July 2010
Asymptotic behavior and long-range interactions in aqueous solutions of poly(ethylene oxide) journal October 1991