Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro

doi:10.1083/jcb.118.3.573

This Article

	Full Text (PDF, 4267K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Wille, H.
	Articles by Mandelkow, E.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Wille, H.
	Articles by Mandelkow, E.


Social Bookmarking

	What's this?

ARTICLES

Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro

H Wille, G Drewes, J Biernat, EM Mandelkow and E Mandelkow
Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.

Recent evidence from several laboratories shows that the paired helical filaments of Alzheimer's disease brains consist mainly of the protein tau in an abnormally phosphorylated form, but the mode of assembly is not understood. Here we use EM to study several constructs derived from human brain tau and expressed in Escherichia coli. All constructs or tau isoforms are rodlike molecules with a high tendency to dimerize in an antiparallel fashion, as shown by antibody labeling and chemical crosslinking. The length of the rods is largely determined by the region of internal repeats that is also responsible for microtubule binding. One unit length of the repeat domain (three or four repeats) is around 22-25 nm, comparable to the cross-section of Alzheimer PHF cores. Constructs corresponding roughly to the repeat region of tau can form synthetic paired helical filaments resembling those from Alzheimer brain tissue. A similar self-assembly occurs with the chemically cross- linked dimers. In both cases there is no need for phosphorylation of the protein.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Wang, Y., Martinez-Vicente, M., Kruger, U., Kaushik, S., Wong, E., Mandelkow, E.-M., Cuervo, A. M., Mandelkow, E. (2009). Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum Mol Genet 18: 4153-4170 [Abstract] [Full Text]
Jeganathan, S., Hascher, A., Chinnathambi, S., Biernat, J., Mandelkow, E.-M., Mandelkow, E. (2008). Proline-directed Pseudo-phosphorylation at AT8 and PHF1 Epitopes Induces a Compaction of the Paperclip Folding of Tau and Generates a Pathological (MC-1) Conformation. J. Biol. Chem. 283: 32066-32076 [Abstract] [Full Text]
Mocanu, M.-M., Nissen, A., Eckermann, K., Khlistunova, I., Biernat, J., Drexler, D., Petrova, O., Schonig, K., Bujard, H., Mandelkow, E., Zhou, L., Rune, G., Mandelkow, E.-M. (2008). The Potential for -Structure in the Repeat Domain of Tau Protein Determines Aggregation, Synaptic Decay, Neuronal Loss, and Coassembly with Endogenous Tau in Inducible Mouse Models of Tauopathy. J. Neurosci. 28: 737-748 [Abstract] [Full Text]
Wang, Y. P., Biernat, J., Pickhardt, M., Mandelkow, E., Mandelkow, E.-M. (2007). Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model. Proc. Natl. Acad. Sci. USA 104: 10252-10257 [Abstract] [Full Text]
Mukrasch, M. D., von Bergen, M., Biernat, J., Fischer, D., Griesinger, C., Mandelkow, E., Zweckstetter, M. (2007). The "Jaws" of the Tau-Microtubule Interaction. J. Biol. Chem. 282: 12230-12239 [Abstract] [Full Text]
Kuhla, B., Haase, C., Flach, K., Luth, H.-J., Arendt, T., Munch, G. (2007). Effect of Pseudophosphorylation and Cross-linking by Lipid Peroxidation and Advanced Glycation End Product Precursors on Tau Aggregation and Filament Formation. J. Biol. Chem. 282: 6984-6991 [Abstract] [Full Text]
Iliev, A. I., Ganesan, S., Bunt, G., Wouters, F. S. (2006). Removal of Pattern-breaking Sequences in Microtubule Binding Repeats Produces Instantaneous Tau Aggregation and Toxicity. J. Biol. Chem. 281: 37195-37204 [Abstract] [Full Text]
Khlistunova, I., Biernat, J., Wang, Y., Pickhardt, M., von Bergen, M., Gazova, Z., Mandelkow, E., Mandelkow, E.-M. (2006). Inducible Expression of Tau Repeat Domain in Cell Models of Tauopathy: AGGREGATION IS TOXIC TO CELLS BUT CAN BE REVERSED BY INHIBITOR DRUGS. J. Biol. Chem. 281: 1205-1214 [Abstract] [Full Text]
Tomoo, K., Yao, T.-M., Minoura, K., Hiraoka, S., Sumida, M., Taniguchi, T., Ishida, T. (2005). Possible Role of Each Repeat Structure of the Microtubule-Binding Domain of the Tau Protein in In Vitro Aggregation. J Biochem 138: 413-423 [Abstract] [Full Text]
Mukrasch, M. D., Biernat, J., von Bergen, M., Griesinger, C., Mandelkow, E., Zweckstetter, M. (2005). Sites of Tau Important for Aggregation Populate {beta}-Structure and Bind to Microtubules and Polyanions. J. Biol. Chem. 280: 24978-24986 [Abstract] [Full Text]
Papanikolopoulou, K., Schoehn, G., Forge, V., Forsyth, V. T., Riekel, C., Hernandez, J.-F., Ruigrok, R. W. H., Mitraki, A. (2005). Amyloid Fibril Formation from Sequences of a Natural {beta}-Structured Fibrous Protein, the Adenovirus Fiber. J. Biol. Chem. 280: 2481-2490 [Abstract] [Full Text]
Margittai, M., Langen, R. (2004). Template-assisted filament growth by parallel stacking of tau. Proc. Natl. Acad. Sci. USA 101: 10278-10283 [Abstract] [Full Text]
AVILA, J., LUCAS, J. J., PEREZ, M., HERNANDEZ, F. (2004). Role of Tau Protein in Both Physiological and Pathological Conditions. Physiol. Rev. 84: 361-384 [Abstract] [Full Text]
Juszczak, L. J. (2004). Comparative Vibrational Spectroscopy of Intracellular Tau and Extracellular Collagen I Reveals Parallels of Gelation and Fibrillar Structure. J. Biol. Chem. 279: 7395-7404 [Abstract] [Full Text]
Makrides, V., Shen, T. E., Bhatia, R., Smith, B. L., Thimm, J., Lal, R., Feinstein, S. C. (2003). Microtubule-dependent Oligomerization of Tau: IMPLICATIONS FOR PHYSIOLOGICAL TAU FUNCTION AND TAUOPATHIES. J. Biol. Chem. 278: 33298-33304 [Abstract] [Full Text]
Yao, T.-M., Tomoo, K., Ishida, T., Hasegawa, H., Sasaki, M., Taniguchi, T. (2003). Aggregation Analysis of the Microtubule Binding Domain in Tau Protein by Spectroscopic Methods. J Biochem 134: 91-99 [Abstract] [Full Text]
Li, L., von Bergen, M., Mandelkow, E.-M., Mandelkow, E. (2002). Structure, Stability, and Aggregation of Paired Helical Filaments from Tau Protein and FTDP-17 Mutants Probed by Tryptophan Scanning Mutagenesis. J. Biol. Chem. 277: 41390-41400 [Abstract] [Full Text]
Sato, S., Tatebayashi, Y., Akagi, T., Chui, D.-H., Murayama, M., Miyasaka, T., Planel, E., Tanemura, K., Sun, X., Hashikawa, T., Yoshioka, K., Ishiguro, K., Takashima, A. (2002). Aberrant Tau Phosphorylation by Glycogen Synthase Kinase-3beta and JNK3 Induces Oligomeric Tau Fibrils in COS-7 Cells. J. Biol. Chem. 277: 42060-42065 [Abstract] [Full Text]
Miake, H., Mizusawa, H., Iwatsubo, T., Hasegawa, M. (2002). Biochemical Characterization of the Core Structure of alpha -Synuclein Filaments. J. Biol. Chem. 277: 19213-19219 [Abstract] [Full Text]
von Bergen, M., Barghorn, S., Li, L., Marx, A., Biernat, J., Mandelkow, E.-M., Mandelkow, E. (2001). Mutations of Tau Protein in Frontotemporal Dementia Promote Aggregation of Paired Helical Filaments by Enhancing Local beta -Structure. J. Biol. Chem. 276: 48165-48174 [Abstract] [Full Text]
Hutton, M. (2001). Missense and splice site mutations in tau associated with FTDP-17: Multiple pathogenic mechanisms. Neurology 56: S21-25 [Abstract] [Full Text]
Alonso, A. d. C., Zaidi, T., Novak, M., Grundke-Iqbal, I., Iqbal, K. (2001). Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA 10.1073/pnas.121119298v1 [Abstract] [Full Text]
Hall, G. F., Lee, V. M.-Y., Lee, G., Yao, J. (2001). Staging of Neurofibrillary Degeneration Caused by Human Tau Overexpression in a Unique Cellular Model of Human Tauopathy. Am. J. Pathol. 158: 235-246 [Abstract] [Full Text]
von Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E.-M., Mandelkow, E. (2000). Assembly of tau protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming beta structure. Proc. Natl. Acad. Sci. USA 97: 5129-5134 [Abstract] [Full Text]
Scheel, J., Pierre, P., Rickard, J. E., Diamantopoulos, G. S., Valetti, C., van der Goot, F. G., Haner, M., Aebi, U., Kreis, T. E. (1999). Purification and Analysis of Authentic CLIP-170 and Recombinant Fragments. J. Biol. Chem. 274: 25883-25891 [Abstract] [Full Text]
Watanabe, A., Takio, K., Ihara, Y. (1999). Deamidation and Isoaspartate Formation in Smeared Tau in Paired Helical Filaments. UNUSUAL PROPERTIES OF THE MICROTUBULE-BINDING DOMAIN OF TAU. J. Biol. Chem. 274: 7368-7378 [Abstract] [Full Text]
Goedert, M., Hasegawa, M. (1999). The Tauopathies : Toward an Experimental Animal Model. Am. J. Pathol. 154: 1-6 [Full Text]
Brion, J.-P., Tremp, G., Octave, J.-N. (1999). Transgenic Expression of the Shortest Human Tau Affects Its Compartmentalization and Its Phosphorylation as in the Pretangle Stage of Alzheimer's Disease. Am. J. Pathol. 154: 255-270 [Abstract] [Full Text]
Friedhoff, P., von Bergen, M., Mandelkow, E.-M., Davies, P., Mandelkow, E. (1998). A nucleated assembly mechanism of Alzheimer paired helical filaments. Proc. Natl. Acad. Sci. USA 95: 15712-15717 [Abstract] [Full Text]
Kawamata, T., Taniguchi, T., Mukai, H., Kitagawa, M., Hashimoto, T., Maeda, K., Ono, Y., Tanaka, C. (1998). A Protein Kinase, PKN, Accumulates in Alzheimer Neurofibrillary Tangles and Associated Endoplasmic Reticulum-Derived Vesicles and Phosphorylates Tau Protein. J. Neurosci. 18: 7402-7410 [Abstract] [Full Text]
Paudel, H. K. (1997). Phosphorylation by Neuronal cdc2-like Protein Kinase Promotes Dimerization of Tau Protein in Vitro. J. Biol. Chem. 272: 28328-28334 [Abstract] [Full Text]
Hall, G. F., Yao, J., Lee, G. (1997). Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons�in�situ. Proc. Natl. Acad. Sci. USA 94: 4733-4738 [Abstract] [Full Text]
Goedert, M. (1997). The Neurofibrillary Pathology of Alzheimer's Disease. Neuroscientist 3: 131-141 [Abstract]
Preuss, U, Biernat, J, Mandelkow, E., Mandelkow, E (1997). The 'jaws' model of tau-microtubule interaction examined in CHO cells. J. Cell Sci. 110: 789-800 [Abstract]
Goedert, M., Spillantini, M.G., Hasegawa, M., Jakes, R., Crowther, R.A., Klug, A. (1996). Molecular Dissection of the Neurofibrillary Lesions of Alzheimer's Disease. Cold Spring Harb Symp Quant Biol 61: 565-573 [Abstract]
Wilson, D. M., Binder, L. I. (1995). Polymerization of Microtubule-associated Protein Tau under Near-physiological Conditions. J. Biol. Chem. 270: 24306-24314 [Abstract] [Full Text]
Seubert, P., Mawal-Dewan, M., Barbour, R., Jakes, R., Goedert, M., Johnson, G. V. W., Litersky, J. M., Schenk, D., Lieberburg, I., Trojanowski, J. Q., Lee, V. M.-Y. (1995). Detection of Phosphorylated Ser[IMAGE] in Fetal Tau, Adult Tau, and Paired Helical Filament Tau. J. Biol. Chem. 270: 18917-18922 [Abstract] [Full Text]
Drewes, G., Trinczek, B., Illenberger, S., Biernat, J., Schmitt-Ulms, G., Meyer, H. E., Mandelkow, E.-M., Mandelkow, E. (1995). Microtubule-associated Protein/Microtubule Affinity-regulating Kinase (p110[IMAGE]). J. Biol. Chem. 270: 7679-7688 [Abstract] [Full Text]
Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Yoshida, H., Titani, K., Ihara, Y. (1995). Proline-directed and Non-proline-directed Phosphorylation of PHF-tau. J. Biol. Chem. 270: 823-829 [Abstract] [Full Text]
Sadot, E, Barg, J, Rasouly, D, Lazarovici, P, Ginzburg, I (1995). Short- and long-term mechanisms of tau regulation in PC12 cells. J. Cell Sci. 108: 2857-2864 [Abstract]
Ackmann, M., Wiech, H., Mandelkow, E. (2000). Nonsaturable Binding Indicates Clustering of Tau on the Microtubule Surface in a Paired Helical Filament-like Conformation. J. Biol. Chem. 275: 30335-30343 [Abstract] [Full Text]
Goode, B. L., Chau, M., Denis, P. E., Feinstein, S. C. (2000). Structural and Functional Differences between 3-Repeat and 4-Repeat Tau Isoforms. IMPLICATIONS FOR NORMAL TAU FUNCTION AND THE ONSET OF NEURODEGENERATIVE DISEASE. J. Biol. Chem. 275: 38182-38189 [Abstract] [Full Text]
Alonso, A. d. C., Zaidi, T., Novak, M., Grundke-Iqbal, I., Iqbal, K. (2001). Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl. Acad. Sci. USA 98: 6923-6928 [Abstract] [Full Text]