Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Chung, Peter J.; Choi, Myung Chul; Miller, Herbert P.; Feinstein, H. Eric; Raviv, Uri; Li, Youli; Wilson, Leslie; Feinstein, Stuart C.; Safinya, Cyrus R.

doi:10.1073/pnas.1513172112

Title: Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Journal Article · Thu Nov 05 00:00:00 EST 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1513172112· OSTI ID:1235187

Chung, Peter J.; Choi, Myung Chul; Miller, Herbert P.; Feinstein, H. Eric; Raviv, Uri; Li, Youli; Wilson, Leslie; Feinstein, Stuart C.; Safinya, Cyrus R.

Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer’s. We report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau isoforms by synchrotron small-angle X-ray scattering (SAXS) of MT-Tau mixtures under osmotic pressure (P). In going from bare MTs to MTs with Tau coverage near the physiological submonolayer regime (Tau/tubulin-dimer molar ratio; Φ_Tau = 1/10), isoforms with longer N-terminal tails (NTTs) sterically stabilized MTs, preventing bundling up to P_B ~ 10,000–20,000 Pa, an order of magnitude larger than bare MTs. Tau with short NTTs showed little additional effect in suppressing the bundling pressure (P_B ~ 1,000–2,000 Pa) over the same range. Remarkably, the abrupt increase in P_B observed for longer isoforms suggests a mushroom to brush transition occurring at 1/13 < Φ_Tau < 1/10, which corresponds to MT-bound Tau with NTTs that are considerably more extended than SAXS data for Tau in solution indicate. Modeling of Tau-mediated MT–MT interactions supports the hypothesis that longer NTTs transition to a polyelectrolyte brush at higher coverages. Higher pressures resulted in isoform-independent irreversible bundling because the polyampholytic nature of Tau leads to short-range attractions. These findings suggest an isoform-dependent biological role for regulation by Tau, with longer isoforms conferring MT steric stabilization against aggregation either with other biomacromolecules or into tight bundles, preventing loss of function in the crowded axon environment.

View Journal Article

Cite

Export

Save

Research Organization:: Univ. of California, Santa Barbara, CA (United States); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; National Science Foundation (NSF); National Institutes of Health (NIH); National Research Foundation of Korea (NRF); Israel Science Foundation (ISF); United States-Israel Binational Science Foundation (BSF)

Grant/Contract Number:: FG02-06ER46314; DMR-1401784; R01-NS13560; R01-NS35010; 2011-0031931; 2014-R1A1A2A16055715; 1565/13; 2009271

OSTI ID:: 1235187

Alternate ID(s):: OSTI ID: 1469100

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 112 Journal Issue: 47; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 37 works

Citation information provided by
Web of Science

References (70)

Gel-expanded to gel-condensed transition in neurofilament networks revealed by direct force measurements Beck, Roy; Deek, Joanna; Jones, Jayna B. Nature Materials, Vol. 9, Issue 1 https://doi.org/10.1038/nmat2566	journal	November 2009
Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains Himmler, A.; Drechsel, D.; Kirschner, M. W. Molecular and Cellular Biology, Vol. 9, Issue 4 https://doi.org/10.1128/mcb.9.4.1381-1388.1989	journal	April 1989
Mutation-Specific Functional Impairments in Distinct Tau Isoforms of Hereditary FTDP-17 Hong, M. Science, Vol. 282, Issue 5395 https://doi.org/10.1126/science.282.5395.1914	journal	December 1998
A protein factor essential for microtubule assembly. Weingarten, M. D.; Lockwood, A. H.; Hwo, S. Y. Proceedings of the National Academy of Sciences, Vol. 72, Issue 5 https://doi.org/10.1073/pnas.72.5.1858	journal	May 1975
Microtubule Protofilament Number Is Modulated in a Stepwise Fashion by the Charge Density of an Enveloping Layer Raviv, Uri; Nguyen, Toan; Ghafouri, Rouzbeh Biophysical Journal, Vol. 92, Issue 1 https://doi.org/10.1529/biophysj.106.087478	journal	January 2007
Tau protein binding forms a 1nm thick layer along protofilaments without affecting the radial elasticity of microtubules Schaap, Iwan A. T.; Hoffmann, Bernd; Carrasco, Carolina Journal of Structural Biology, Vol. 158, Issue 3 https://doi.org/10.1016/j.jsb.2006.11.010	journal	June 2007
A Hypothesis on the Origin and Evolution of Tubulin Ludueña, Richard F. International Review of Cell and Molecular Biology https://doi.org/10.1016/B978-0-12-407699-0.00002-9	book	January 2013
Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Drechsel, D. N.; Hyman, A. A.; Cobb, M. H. Molecular Biology of the Cell, Vol. 3, Issue 10 https://doi.org/10.1091/mbc.3.10.1141	journal	October 1992
Interplay between Liquid Crystalline and Isotropic Gels in Self-Assembled Neurofilament Networks Jones, Jayna B.; Safinya, Cyrus R. Biophysical Journal, Vol. 95, Issue 2 https://doi.org/10.1529/biophysj.107.127415	journal	July 2008
Transformation of taxol-stabilized microtubules into inverted tubulin tubules triggered by a tubulin conformation switch Ojeda-Lopez, Miguel A.; Needleman, Daniel J.; Song, Chaeyeon Nature Materials, Vol. 13, Issue 2 https://doi.org/10.1038/nmat3858	journal	January 2014
Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability Esmaeli-Azad, B.; McCarty, J. H.; Feinstein, S. C. Journal of Cell Science, Vol. 107, Issue 4 https://doi.org/10.1242/jcs.107.4.869	journal	April 1994
Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. Schweers, O.; Schönbrunn-Hanebeck, E.; Marx, A. Journal of Biological Chemistry, Vol. 269, Issue 39 https://doi.org/10.1016/S0021-9258(19)51080-8	journal	September 1994
The distribution of tau in the mammalian central nervous system Binder, L. I. The Journal of Cell Biology, Vol. 101, Issue 4 https://doi.org/10.1083/jcb.101.4.1371	journal	October 1985
Composite bottlebrush mechanics: α-internexin fine-tunes neurofilament network properties Kornreich, M.; Malka-Gibor, E.; Laser-Azogui, A. Soft Matter, Vol. 11, Issue 29 https://doi.org/10.1039/C5SM00662G	journal	January 2015
Assembly of Biological Nanostructures: Isotropic and Liquid Crystalline Phases of Neurofilament Hydrogels Safinya, Cyrus R.; Deek, Joanna; Beck, Roy Annual Review of Condensed Matter Physics, Vol. 6, Issue 1 https://doi.org/10.1146/annurev-conmatphys-031214-014623	journal	March 2015
Synchrotron X-ray Diffraction Study of Microtubules Buckling and Bundling under Osmotic Stress: A Probe of Interprotofilament Interactions Needleman, Daniel J.; Ojeda-Lopez, Miguel A.; Raviv, Uri Physical Review Letters, Vol. 93, Issue 19 https://doi.org/10.1103/PhysRevLett.93.198104	journal	November 2004
Assembly and structure of neurofilaments Janmey, Paul A.; Leterrier, Jean-Francois; Herrmann, Harald Current Opinion in Colloid & Interface Science, Vol. 8, Issue 1 https://doi.org/10.1016/S1359-0294(03)00010-4	journal	March 2003
Electrophoresis of individual microtubules in microchannels van den Heuvel, M. G. L.; de Graaff, M. P.; Lemay, S. G. Proceedings of the National Academy of Sciences, Vol. 104, Issue 19 https://doi.org/10.1073/pnas.0608316104	journal	April 2007
Monte Carlo Simulations of Tau Proteins: Effect of Phosphorylation Jho, Y. S.; Zhulina, E. B.; Kim, M. W. Biophysical Journal, Vol. 99, Issue 8 https://doi.org/10.1016/j.bpj.2010.06.056	journal	October 2010
Substoichiometric Binding of Taxol Suppresses Microtubule Dynamics Derry, W. Brent; Wilson, Leslie; Jordan, Mary Ann Biochemistry, Vol. 34, Issue 7 https://doi.org/10.1021/bi00007a014	journal	February 1995
Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Kosik, K. S.; Joachim, C. L.; Selkoe, D. J. Proceedings of the National Academy of Sciences, Vol. 83, Issue 11 https://doi.org/10.1073/pnas.83.11.4044	journal	June 1986
Electrostatic interaction between two cylindrical soft particles Ohshima, Hiroyuki; Hyono, Atsushi Journal of Colloid and Interface Science, Vol. 333, Issue 1 https://doi.org/10.1016/j.jcis.2008.11.060	journal	May 2009
The three-dimensional structure of tubulin protofilaments Amos, L. A.; Baker, T. S. Nature, Vol. 279, Issue 5714 https://doi.org/10.1038/279607a0	journal	June 1979
Projection domains of MAP2 and tau determine spacings between microtubules in dendrites and axons Chen, J.; Kanai, Y.; Cowan, N. J. Nature, Vol. 360, Issue 6405 https://doi.org/10.1038/360674a0	journal	December 1992
Low resolution structure of microtubules in solution Andreu, J. M.; Bordas, J.; Diaz, J. F. Journal of Molecular Biology, Vol. 226, Issue 1 https://doi.org/10.1016/0022-2836(92)90132-4	journal	July 1992
Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury McKee, Ann C.; Cantu, Robert C.; Nowinski, Christopher J. Journal of Neuropathology & Experimental Neurology, Vol. 68, Issue 7 https://doi.org/10.1097/NEN.0b013e3181a9d503	journal	July 2009
The microtubule binding domain of tau protein Lee, Gloria; Neve, Rachael L.; Kosik, Kenneth S. Neuron, Vol. 2, Issue 6 https://doi.org/10.1016/0896-6273(89)90050-0	journal	June 1989
The Many Faces of Tau Morris, Meaghan; Maeda, Sumihiro; Vossel, Keith Neuron, Vol. 70, Issue 3 https://doi.org/10.1016/j.neuron.2011.04.009	journal	May 2011
Tau stabilizes microtubules by binding at the interface between tubulin heterodimers Kadavath, Harindranath; Hofele, Romina V.; Biernat, Jacek Proceedings of the National Academy of Sciences, Vol. 112, Issue 24 https://doi.org/10.1073/pnas.1504081112	journal	June 2015
Microtubule Polymerization Dynamics Desai, Arshad; Mitchison, Timothy J. Annual Review of Cell and Developmental Biology, Vol. 13, Issue 1 https://doi.org/10.1146/annurev.cellbio.13.1.83	journal	November 1997
The Conformational Ensembles of α-Synuclein and Tau: Combining Single-Molecule FRET and Simulations Nath, Abhinav; Sammalkorpi, Maria; DeWitt, David C. Biophysical Journal, Vol. 103, Issue 9 https://doi.org/10.1016/j.bpj.2012.09.032	journal	November 2012
Modeling of the 3RS tau protein with self-consistent field method and Monte Carlo simulation Leermakers, F. A. M.; Jho, Y. -S.; Zhulina, E. B. Soft Matter, Vol. 6, Issue 21 https://doi.org/10.1039/c0sm00191k	journal	January 2010
Developmentally regulated expression of specific tau sequences Kosik, Kenneth S.; Orecchio, Lisa D.; Bakalis, Shelley Neuron, Vol. 2, Issue 4 https://doi.org/10.1016/0896-6273(89)90077-9	journal	April 1989
Equilibrium distribution of flexible polymer chains between a macroscopic solution phase and small voids Casassa, Edward F. Journal of Polymer Science Part B: Polymer Letters, Vol. 5, Issue 9 https://doi.org/10.1002/pol.1967.110050907	journal	September 1967
Structure and Viscosity of Interpenetrating Polyelectrolyte Chains Witten, T. A.; Pincus, P. Europhysics Letters (EPL), Vol. 3, Issue 3 https://doi.org/10.1209/0295-5075/3/3/011	journal	February 1987
Alzheimer Mechanisms and Therapeutic Strategies Huang, Yadong; Mucke, Lennart Cell, Vol. 148, Issue 6 https://doi.org/10.1016/j.cell.2012.02.040	journal	March 2012
Structural memory of natively unfolded tau protein detected by small-angle X-ray scattering Shkumatov, Alexander V.; Chinnathambi, Subashchandrabose; Mandelkow, Eckhard Proteins: Structure, Function, and Bioinformatics, Vol. 79, Issue 7 https://doi.org/10.1002/prot.23033	journal	May 2011
Differential regulation of microtubule dynamics by three- and four-repeat tau: Implications for the onset of neurodegenerative disease Panda, D.; Samuel, J. C.; Massie, M. Proceedings of the National Academy of Sciences, Vol. 100, Issue 16 https://doi.org/10.1073/pnas.1633508100	journal	July 2003
Nerve growth factor-induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors Drubin, D. G. The Journal of Cell Biology, Vol. 101, Issue 5 https://doi.org/10.1083/jcb.101.5.1799	journal	November 1985
Random-coil behavior and the dimensions of chemically unfolded proteins Kohn, J. E.; Millett, I. S.; Jacob, J. Proceedings of the National Academy of Sciences, Vol. 101, Issue 34 https://doi.org/10.1073/pnas.0403643101	journal	August 2004
Tau Is Enriched on Dynamic Microtubules in the Distal Region of Growing Axons Black, Mark M.; Slaughter, Theresa; Moshiach, Simon The Journal of Neuroscience, Vol. 16, Issue 11 https://doi.org/10.1523/JNEUROSCI.16-11-03601.1996	journal	June 1996
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17 Hutton, Mike; Lendon, Corinne L.; Rizzu, Patrizia Nature, Vol. 393, Issue 6686 https://doi.org/10.1038/31508	journal	June 1998
Tau protein binds to microtubules through a flexible array of distributed weak sites Butner, K. A. The Journal of Cell Biology, Vol. 115, Issue 3 https://doi.org/10.1083/jcb.115.3.717	journal	November 1991
Molecular dynamics simulations of tubulin structure and calculations of electrostatic properties of microtubules Tuszyński, J. A.; Brown, J. A.; Crawford, E. Mathematical and Computer Modelling, Vol. 41, Issue 10 https://doi.org/10.1016/j.mcm.2005.05.002	journal	May 2005
From The Cover: Higher-order assembly of microtubules by counterions: From hexagonal bundles to living necklaces Needleman, D. J.; Ojeda-Lopez, M. A.; Raviv, U. Proceedings of the National Academy of Sciences, Vol. 101, Issue 46 https://doi.org/10.1073/pnas.0406076101	journal	November 2004
Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17 Clark, L. N.; Poorkaj, P.; Wszolek, Z. Proceedings of the National Academy of Sciences, Vol. 95, Issue 22 https://doi.org/10.1073/pnas.95.22.13103	journal	October 1998
The primary structure and heterogeneity of tau protein from mouse brain Lee, G.; Cowan, N.; Kirschner, M. Science, Vol. 239, Issue 4837 https://doi.org/10.1126/science.3122323	journal	January 1988
Concentration and Solvency Effects on the Pair Interaction between Colloidal Particles in a Solution of Nonadsorbing Polymer Tuinier, Remco; Fleer, Gerard J. Macromolecules, Vol. 37, Issue 23 https://doi.org/10.1021/ma048571p	journal	November 2004
Human Microtubule-Associated-Protein Tau Regulates the Number of Protofilaments in Microtubules: A Synchrotron X-Ray Scattering Study Choi, M. C.; Raviv, U.; Miller, H. P. Biophysical Journal, Vol. 97, Issue 2 https://doi.org/10.1016/j.bpj.2009.04.047	journal	July 2009
Domain Conformation of Tau Protein Studied by Solution Small-Angle X-ray Scattering ^† Mylonas, Efstratios; Hascher, Antje; Bernadó, Pau Biochemistry, Vol. 47, Issue 39 https://doi.org/10.1021/bi800900d	journal	September 2008
Refined structure of αβ-tubulin at 3.5 Å resolution 1 1Edited by I. A. Wilson Löwe, J.; Li, H.; Downing, K. H. Journal of Molecular Biology, Vol. 313, Issue 5 https://doi.org/10.1006/jmbi.2001.5077	journal	November 2001
Interactions between sickle hemoglobin fibers Jones, Christopher W.; Wang, Jiang Cheng; Ferrone, Frank A. Faraday Discussions, Vol. 123 https://doi.org/10.1039/b207388a	journal	September 2002
Regulation and aggregation of intrinsically disordered peptides Levine, Zachary A.; Larini, Luca; LaPointe, Nichole E. Proceedings of the National Academy of Sciences, Vol. 112, Issue 9 https://doi.org/10.1073/pnas.1418155112	journal	February 2015
Radial Compression of Microtubules and the Mechanism of Action of Taxol and Associated Proteins Needleman, Daniel J.; Ojeda-Lopez, Miguel A.; Raviv, Uri Biophysical Journal, Vol. 89, Issue 5 https://doi.org/10.1529/biophysj.104.057679	journal	November 2005
Kinetic stabilization of microtubule dynamic instability in vitro by vinblastine Toso, Robert J.; Jordan, Mary Ann; Farrell, Kevin W. Biochemistry, Vol. 32, Issue 5 https://doi.org/10.1021/bi00056a013	journal	February 1993
The interaction between two cylinder shaped colloidal particles Sparnaay, M. J. Recueil des Travaux Chimiques des Pays-Bas, Vol. 78, Issue 9 https://doi.org/10.1002/recl.19590780908	journal	January 1959
Tubulin requires tau for growth onto microtubule initiating sites. Witman, G. B.; Cleveland, D. W.; Weingarten, M. D. Proceedings of the National Academy of Sciences, Vol. 73, Issue 11 https://doi.org/10.1073/pnas.73.11.4070	journal	November 1976
Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau Goode, B. L. The Journal of Cell Biology, Vol. 124, Issue 5 https://doi.org/10.1083/jcb.124.5.769	journal	March 1994
Structure of tubulin at 6.5 Å and location of the taxol-binding site Nogales, Eva; Grayer Wolf, Sharon; Khan, Israr A. Nature, Vol. 375, Issue 6530 https://doi.org/10.1038/375424a0	journal	June 1995
Statistics of macromolecular solutions trapped in small pores Daoud, M.; De Gennes, P. G. Journal de Physique, Vol. 38, Issue 1 https://doi.org/10.1051/jphys:0197700380108500	journal	January 1977
Domains of tau Protein and Interactions with Microtubules Gustke, N.; Trinczek, B.; Biernat, J. Biochemistry, Vol. 33, Issue 32 https://doi.org/10.1021/bi00198a017	journal	October 1994
Colloid stabilization with grafted polyelectrolytes Pincus, Philip Macromolecules, Vol. 24, Issue 10 https://doi.org/10.1021/ma00010a043	journal	May 1991
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia Spillantini, M. G.; Murrell, J. R.; Goedert, M. Proceedings of the National Academy of Sciences, Vol. 95, Issue 13 https://doi.org/10.1073/pnas.95.13.7737	journal	June 1998
Microtubule bundling by tau proteins in vivo: analysis of functional domains. Kanai, Y.; Chen, J.; Hirokawa, N. The EMBO Journal, Vol. 11, Issue 11 https://doi.org/10.1002/j.1460-2075.1992.tb05489.x	journal	November 1992
Cationic liposome-microtubule complexes: Pathways to the formation of two-state lipid-protein nanotubes with open or closed ends Raviv, U.; Needleman, D. J.; Li, Y. Proceedings of the National Academy of Sciences, Vol. 102, Issue 32 https://doi.org/10.1073/pnas.0502183102	journal	July 2005
An improved fit to Website osmotic pressure data Cohen, J. A.; Highsmith, S. Biophysical Journal, Vol. 73, Issue 3 https://doi.org/10.1016/S0006-3495(97)78200-6	journal	September 1997
Adsorption of Hydrophobic Polyelectrolytes at Oppositely Charged Surfaces Dobrynin, Andrey V.; Rubinstein, Michael Macromolecules, Vol. 35, Issue 7 https://doi.org/10.1021/ma0114943	journal	March 2002
Microtubule orientation and spacing within bundles is critical for long-range kinesin-1 motility: Microtubule Bundles Architecture Affects Kinesin-1 Motility Conway, Leslie; Gramlich, Michael W.; Ali Tabei, S. M. Cytoskeleton, Vol. 71, Issue 11 https://doi.org/10.1002/cm.21197	journal	November 2014
Straight GDP-Tubulin Protofilaments Form in the Presence of Taxol Elie-Caille, Céline; Severin, Fedor; Helenius, Jonne Current Biology, Vol. 17, Issue 20 https://doi.org/10.1016/j.cub.2007.08.063	journal	October 2007
Asymptotic behavior and long-range interactions in aqueous solutions of poly(ethylene oxide) Devanand, K.; Selser, J. C. Macromolecules, Vol. 24, Issue 22 https://doi.org/10.1021/ma00022a008	journal	October 1991

Similar Records

Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment

Journal Article · Mon Jul 25 00:00:00 EDT 2016 · Nature Communications · OSTI ID:1235187

Chung, Peter J.; Song, Chaeyeon; Deek, Joanna; +6 more

Complexes of tubulin oligomers and tau form a viscoelastic intervening network cross-bridging microtubules into bundles

Journal Article · Fri Mar 15 00:00:00 EDT 2024 · Nature Communications · OSTI ID:1235187

Kohl, Phillip A.; Song, Chaeyeon; Fletcher, Bretton J.; +10 more

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

Journal Article · Fri Sep 20 00:00:00 EDT 2019 · Langmuir · OSTI ID:1235187

Safinya, Cyrus R.; Chung, Peter J.; Song, Chaeyeon; +7 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Tau
intrinsically disordered proteins
microtubule
SAXS
force measurement

Title: Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

Citation Formats

References (70)

Similar Records

Related Subjects