The microtubule binding repeats of tau protein assemble into filaments like those found in Alzheimer's disease
FEBS LettersPublished 7 September 1992
R. Anthony Crowther, Ole F. Olesen, Ross Jakes, Michel Goedert
Citations168
SJR quartileQ1
SJR score1.22
SNIP0.77
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TL;DR
It is shown that an expressed fragment of tau protein spanning the repeat region can assemble in vitro into filaments like those found in Alzheimer's disease.
Abstract
The paired helical filament, which comprises the major fibrous element of the neurofibrillary tangle in Alzheimer's disease, contains abnormally phosphorylated microtubule-associated protein tau as its principal constituent. The repeat region of tau protein, which represents the microtubule binding domain, forms the core of the filament. Here we show that an expressed fragment of tau protein spanning the repeat region can assemble in vitro into filaments like those found in Alzheimer's disease.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
NeuronMultiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
2,464 Citations1989Michel Goedert, Maria Grazia Spillantini +3 more
Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease.
ScienceA68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
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The major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68.
Proceedings of the National Academy of SciencesCloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau.
1,139 Citations1988Michel Goedert, Claude M. Wischik +3 more
The proof that at least part of tau protein forms a component of the paired helical filament core opens the way to understanding the mode of formation of paired helicals filaments and thus, ultimately, the pathogenesis of Alzheimer disease.
NeuronTau proteins of alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms
1,133 Citations1992Michel Goedert, Maria Grazia Spillantini +2 more
By using antibodies specific for some of the inserts that distinguish the various isoforms and label PHFs, a correspondence betweenPHFs, abnormal bands, and isoforms is established and is a necessary step in unravelling the molecular pathogenesis of PHFs.
The EMBO JournalCloning and sequencing of the cDNA encoding an isoform of microtubule‐associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain.
1,029 Citations1989Michel Goedert, Maria Grazia Spillantini +3 more
Tau protein is found in the protease‐resistant core of the paired helical filament, the major constituent of the neurofibrillary tangle in Alzheimer's disease.
NaturePaired Helical Filaments in Electron Microscopy of Alzheimer's Disease
976 Citations1963M.T. Kidd
Well-known findings would lead one to expect the presence of fine filaments associated with these cells in the electron microscope, and if intra-cellular, these might be neurofilaments, which are suggested by Gray and Guillery2 to be the basis of neurofibrillary argyro-philia.
Proceedings of the National Academy of SciencesIsolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.
944 Citations1988Claude M. Wischik, M Novák +8 more
A substantially enriched preparation of Alzheimer paired helical filaments has been used as a starting point for biochemical studies and sequence analysis of these peptides was used to design oligonucleotide probes for cloning a cognate cDNA, which leads to its identification as human microtubule-associated tau protein.
The EMBO JournalExpression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization.
924 Citations1990Michel Goedert, Ross Jakes
The recombinant tau isoforms were biologically active at micromolar concentrations, as assessed by their ability to promote microtubule assembly and the rates of assembly were 2.5–3.0 times faster for isoforms containing four repeats when compared with three‐repeat containing isoforms, with no significant contribution by the amino‐terminal insertions.
Proceedings of the National Academy of SciencesA preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis.
740 Citations1990S G Greenberg, Peter J. Davies
PHF-associated tau can be distinguished from normal, soluble tau by PHF antibodies that do not recognize human adult tau and by one- and two-dimensional PAGE.
Proceedings of the National Academy of SciencesStructural characterization of the core of the paired helical filament of Alzheimer disease.
596 Citations1988Claude M. Wischik, M Novák +4 more
The paired helical filament, the principal constituent of the neurofibrillary tangles characteristic of Alzheimer disease, is shown to consist of two structurally distinct parts, and the mass per unit length measurements imply that the three-domain structural subunit of the core has a molecular mass of approximately equal to 100 kDa.
The Journal of Cell BiologyTau protein binds to microtubules through a flexible array of distributed weak sites.
555 Citations1991Karen A. Butner, Marc W. Kirschner
A collection of tau protein fragments synthesized and studied their binding properties suggest tauprotein can assume multiple conformations and can pivot and perhaps migrate on the surface of the microtubule.
NeuronThe microtubule binding domain of tau protein
493 Citations1989Gloria Lee, Rachael L. Neve +1 more
Determination of tau protein structure has revealed three 18 amino acid repeated sequences hypothesized to be tubulin binding sites, indicating that the basic tubulin interacting unit is one repeat.
The EMBO JournalThe switch of tau protein to an Alzheimer‐like state includes the phosphorylation of two serine‐proline motifs upstream of the microtubule binding region.
480 Citations1992Jacek Biernat, Eckhard Mandelkow� +8 more
It is shown that a new monoclonal antibody, AT8, records the PHF‐like state of tau in vitro, and a kinase activity is described that turns normal tau into a PHF-like state.
HAL (Le Centre pour la Communication Scientifique Directe)Crystallization of Nucleic Acids and Proteins: A practical Approach
387 Citations1998A. Ducruix, Richard Giegé
This work presents an introduction to the crystallogenesis of biological macromolecules by Giege and Ducruix and methods of crystallization and some of the techniques used in this research.
NeuronThe car☐yl third of tau is tightly bound to paired helical filaments
370 Citations1988Jun Kondo, Toshiyuki Honda +5 more
It is concluded that the carboxyl third of tau is tightly bound to PHF.
The Journal of Cell BiologySubunit structure of paired helical filaments in Alzheimer's disease.
225 Citations1985Claude M. Wischik, R. Anthony Crowther +2 more
Observations indicate that the paired helical filament (PHF) consists of subunits of very limited axial extent arranged along two left-handed helical strands, which makes it most unlikely that the PHF is formed by a simple collapse of normal cytoskeletal elements, such as neurofilaments.
The Journal of Cell BiologyTau protein becomes long and stiff upon phosphorylation: correlation between paracrystalline structure and degree of phosphorylation.
189 Citations1989T. Hagestedt, B. Lichtenberg +3 more
This work has shown that microtubule-associated protein tau can be induced to form paracrystals and that this property is related to the state of phosphorylation, which may provide a model for the control of structural properties of tau-like molecules by phosphorylated.
The EMBO JournalImage reconstruction of the Alzheimer paired helical filament.
185 Citations1985R. Anthony Crowther, Claude M. Wischik
These results establish conclusively that the PHF is made up of a double helical stack of transversely oriented subunits, each of which has three domains, and precludes purely descriptive models based on helical rearrangements of preformed cytoskeletal polymers or protofilaments.
The EMBO JournalIdentification of 3‐ and 4‐repeat tau isoforms within the PHF in Alzheimer's disease.
149 Citations1991Ross Jakes, M Novák +2 more
The alignment of cleavage sites at homologous positions within tandem repeats after protease treatment indicates that the tau‐core association is precisely constrained by the tandem repeat structure of the t Tau molecule.
NeuronStructural stability of paired helical filaments requires microtubule-binding domains of Tau: A model for self-association
132 Citations1991Hanna Ksiȩżak-Reding, Shu-Hui Yen
The results and the model of Crowther and Wischik suggest that by self-association and anti-parallel arrangement of the microtubule-binding domains, PHF-tau forms the backbone of PHFs.
Biochemical JournalA68 proteins in Alzheimer's disease are composed of several tau isoforms in a phosphorylated state which affects their electrophoretic mobilities
109 Citations1991Jean‐Pierre Brion, Diane P. Hanger +2 more
The results further support the notion that PHF contain abnormally phosphorylated tau in an aggregated state, and indicate that these abnormally phosphate-filled tau forms are composed of several tau isoforms and that the full length of the tau molecule is present in these polypeptides.
Journal of the Neurological SciencesCharacterization of two pathological Tau protein variants in Alzheimer brain cortices
101 Citations1989Stéphane Flament, A. Delacourte +2 more
Tau 64 and Tau 69 are specific markers of the Alzheimer's disease neuronal degenerating process and their characterization demonstrates that an abnormal phosphorylation of Tau really occurs during the disease.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseStructural aspects of pathology in Alzheimer's disease
55 Citations1990R. Anthony Crowther
The structure of the paired helical filament from tangles has been analysed by electron microscopy and biochemical studies have shown that it contains microtubule associated protein tau as a component.