|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 113, Issue 21 3737-3745, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
A Abraha, N Ghoshal, TC Gamblin, V Cryns, RW Berry, J Kuret and LI Binder
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA. a-abraha@northwestern.edu
Alzheimer's disease (AD) is, in part, defined by the polymerization of tau into paired helical and straight filaments (PHF/SFs) which together comprise the fibrillar pathology in degenerating brain regions. Much of the tau in these filaments is modified by phosphorylation. Additionally, a subset also appears to be proteolytically truncated, resulting in the removal of its C terminus. Antibodies that recognize tau phosphorylated at S(396/404 )or truncated at E(391) do not stain control brains but do stain brain sections very early in the disease process. We modeled these phosphorylation and truncation events by creating pseudo-phosphorylation and deletion mutants derived from a full-length recombinant human tau protein isoform (ht40) that contains N-terminal exons 2 and 3 and all four microtubule-binding repeats. In vitro assembly experiments demonstrate that both modifications greatly enhance the rates of tau filament formation and that truncation increases the mass of polymer formed, as well. Removal of as few as 12 or as many as 121 amino acids from the C terminus of tau greatly increases the rate and extent of tau polymerization. However, deletion of an additional 7 amino acids, (314)DLSKVTS(320), from the third microtubule-binding repeat results in the loss of tau's ability to form filaments in vitro. These results suggest that only part of the microtubule-binding domain (repeats 1, 2 and a small portion of 3) is crucial for tau polymerization. Moreover, the C terminus of tau clearly inhibits the assembly process; this inhibition can be partially reversed by site-specific phosphorylation and completely removed by truncation events at various sites from S(320) to the end of the molecule.
This article has been cited by other articles:
|
|
 |
|
  I. Ferrer, G. Santpere, and F. W. van Leeuwen Argyrophilic grain disease Brain, June 1, 2008; 131(6): 1416 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-S. Cheng, Y.-L. Hsiao, C.-C. Lin, C.-T. R. Yu, C.-M. Hsu, M.-S. Chang, C.-I Lee, C.-Y. F. Huang, S.-L. Howng, and Y.-R. Hong Glycogen Synthase Kinase 3 Interacts with and Phosphorylates the Spindle-associated Protein Astrin J. Biol. Chem., January 25, 2008; 283(4): 2454 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Delobel, I. Lavenir, G. Fraser, E. Ingram, M. Holzer, B. Ghetti, M. G. Spillantini, R. A. Crowther, and M. Goedert Analysis of Tau Phosphorylation and Truncation in a Mouse Model of Human Tauopathy Am. J. Pathol., January 1, 2008; 172(1): 123 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-R. Ryoo, H. K. Jeong, C. Radnaabazar, J.-J. Yoo, H.-J. Cho, H.-W. Lee, I.-S. Kim, Y.-H. Cheon, Y. S. Ahn, S.-H. Chung, et al. DYRK1A-mediated Hyperphosphorylation of Tau: A FUNCTIONAL LINK BETWEEN DOWN SYNDROME AND ALZHEIMER DISEASE J. Biol. Chem., November 30, 2007; 282(48): 34850 - 34857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chun and G. V. W. Johnson Activation of Glycogen Synthase Kinase 3beta Promotes the Intermolecular Association of Tau: THE USE OF FLUORESCENCE RESONANCE ENERGY TRANSFER MICROSCOPY J. Biol. Chem., August 10, 2007; 282(32): 23410 - 23417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. P. Wang, J. Biernat, M. Pickhardt, E. Mandelkow, and E.-M. Mandelkow Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model PNAS, June 12, 2007; 104(24): 10252 - 10257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zibaee, O. S. Makin, M. Goedert, and L. C. Serpell A simple algorithm locates beta-strands in the amyloid fibril core of {alpha}-synuclein, Abeta, and tau using the amino acid sequence alone Protein Sci., May 1, 2007; 16(5): 906 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Margittai and R. Langen Side Chain-dependent Stacking Modulates Tau Filament Structure J. Biol. Chem., December 8, 2006; 281(49): 37820 - 37827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Reynolds, J. F. Reyes, Y. Fu, E. H. Bigio, A. L. Guillozet-Bongaarts, R. W. Berry, and L. I. Binder Tau nitration occurs at tyrosine 29 in the fibrillar lesions of Alzheimer's disease and other tauopathies. J. Neurosci., October 18, 2006; 26(42): 10636 - 10645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ding, T. A. Matthews, and G. V. W. Johnson Site-specific Phosphorylation and Caspase Cleavage Differentially Impact Tau-Microtubule Interactions and Tau Aggregation J. Biol. Chem., July 14, 2006; 281(28): 19107 - 19114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mi, P. J. Dolan, and G. V. W. Johnson The Low Density Lipoprotein Receptor-related Protein 6 Interacts with Glycogen Synthase Kinase 3 and Attenuates Activity J. Biol. Chem., February 24, 2006; 281(8): 4787 - 4794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bhaskar, S.-H. Yen, and G. Lee Disease-related Modifications in Tau Affect the Interaction between Fyn and Tau J. Biol. Chem., October 21, 2005; 280(42): 35119 - 35125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pickhardt, Z. Gazova, M. von Bergen, I. Khlistunova, Y. Wang, A. Hascher, E.-M. Mandelkow, J. Biernat, and E. Mandelkow Anthraquinones Inhibit Tau Aggregation and Dissolve Alzheimer's Paired Helical Filaments in Vitro and in Cells J. Biol. Chem., February 4, 2005; 280(5): 3628 - 3635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Papanikolopoulou, G. Schoehn, V. Forge, V. T. Forsyth, C. Riekel, J.-F. Hernandez, R. W. H. Ruigrok, and A. Mitraki Amyloid Fibril Formation from Sequences of a Natural {beta}-Structured Fibrous Protein, the Adenovirus Fiber J. Biol. Chem., January 28, 2005; 280(4): 2481 - 2490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Stoothoff, J.-H. Cho, R. P. McDonald, and G. V. W. Johnson FRAT-2 Preferentially Increases Glycogen Synthase Kinase 3{beta}-mediated Phosphorylation of Primed Sites, Which Results in Enhanced Tau Phosphorylation J. Biol. Chem., January 7, 2005; 280(1): 270 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Cho and G. V. W. Johnson Glycogen Synthase Kinase 3{beta} Induces Caspase-cleaved Tau Aggregation in Situ J. Biol. Chem., December 24, 2004; 279(52): 54716 - 54723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Necula and J. Kuret Pseudophosphorylation and Glycation of Tau Protein Enhance but Do Not Trigger Fibrillization in Vitro J. Biol. Chem., November 26, 2004; 279(48): 49694 - 49703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. V. W. Johnson and W. H. Stoothoff Tau phosphorylation in neuronal cell function and dysfunction J. Cell Sci., November 15, 2004; 117(24): 5721 - 5729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Horowitz, K. R. Patterson, A. L. Guillozet-Bongaarts, M. R. Reynolds, C. A. Carroll, S. T. Weintraub, D. A. Bennett, V. L. Cryns, R. W. Berry, and L. I. Binder Early N-Terminal Changes and Caspase-6 Cleavage of Tau in Alzheimer's Disease J. Neurosci., September 8, 2004; 24(36): 7895 - 7902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Margittai and R. Langen Template-assisted filament growth by parallel stacking of tau PNAS, July 13, 2004; 101(28): 10278 - 10283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Goux, L. Kopplin, A. D. Nguyen, K. Leak, M. Rutkofsky, V. D. Shanmuganandam, D. Sharma, H. Inouye, and D. A. Kirschner The Formation of Straight and Twisted Filaments from Short Tau Peptides J. Biol. Chem., June 25, 2004; 279(26): 26868 - 26875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. AVILA, J. J. LUCAS, M. PEREZ, and F. HERNANDEZ Role of Tau Protein in Both Physiological and Pathological Conditions Physiol Rev, April 1, 2004; 84(2): 361 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Moreno-Herrero, M. Perez, A. M. Baro, and J. Avila Characterization by Atomic Force Microscopy of Alzheimer Paired Helical Filaments under Physiological Conditions Biophys. J., January 1, 2004; 86(1): 517 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ferrari, F. Hoerndli, T. Baechi, R. M. Nitsch, and J. Gotz {beta}-Amyloid Induces Paired Helical Filament-like Tau Filaments in Tissue Culture J. Biol. Chem., October 10, 2003; 278(41): 40162 - 40168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Gamblin, F. Chen, A. Zambrano, A. Abraha, S. Lagalwar, A. L. Guillozet, M. Lu, Y. Fu, F. Garcia-Sierra, N. LaPointe, et al. Caspase cleavage of tau: Linking amyloid and neurofibrillary tangles in Alzheimer's disease PNAS, August 19, 2003; 100(17): 10032 - 10037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, M. von Bergen, E.-M. Mandelkow, and E. Mandelkow Structure, Stability, and Aggregation of Paired Helical Filaments from Tau Protein and FTDP-17 Mutants Probed by Tryptophan Scanning Mutagenesis J. Biol. Chem., October 25, 2002; 277(44): 41390 - 41400. [Abstract] [Full Text] [PDF]
|
|
