Journal ArticleDOI
Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates.
Melina Theoni Gyparaki,Arian Arab,Elena M. Sorokina,Adriana N. Santiago-Ruiz,Christopher H. Bohrer,Jie Xiao,Melike Lakadamyali +6 more
TLDR
In this article, the spatial distribution of tau monomers and oligomers inside cells under physiological or pathological conditions has not been visualized, and the authors showed that tau forms small oligomers on microtubules ex vivo.Abstract:
Tau is a microtubule-associated protein, which promotes neuronal microtubule assembly and stability. Accumulation of tau into insoluble aggregates known as neurofibrillary tangles (NFTs) is a pathological hallmark of several neurodegenerative diseases. The current hypothesis is that small, soluble oligomeric tau species preceding NFT formation cause toxicity. However, thus far, visualizing the spatial distribution of tau monomers and oligomers inside cells under physiological or pathological conditions has not been possible. Here, using single-molecule localization microscopy, we show that tau forms small oligomers on microtubules ex vivo. These oligomers are distinct from those found in cells exhibiting tau aggregation and could be precursors of aggregated tau in pathology. Furthermore, using an unsupervised shape classification algorithm that we developed, we show that different tau phosphorylation states are associated with distinct tau aggregate species. Our work elucidates tau's nanoscale composition under nonaggregated and aggregated conditions ex vivo.read more
Citations
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Journal ArticleDOI
Single-molecule localization microscopy
Mickaël Lelek,Mickaël Lelek,Melina Theoni Gyparaki,Gerti Beliu,Florian Schueder,Florian Schueder,Juliette Griffié,Suliana Manley,Ralf Jungmann,Ralf Jungmann,Markus Sauer,Melike Lakadamyali,Christophe Zimmer,Christophe Zimmer +13 more
TL;DR: This Primer explains the central concepts of single-molecule localization microscopy before discussing experimental considerations regarding fluorophores, optics and data acquisition, processing and analysis, and describes recent high-impact discoveries made by SMLM techniques.
Journal ArticleDOI
Liquid-liquid phase separation of tau: From molecular biophysics to physiology and disease.
Sandeep K. Rai,Adriana Savastano,Priyanka Singh,Samrat Mukhopadhyay,Markus Zweckstetter,Markus Zweckstetter +5 more
TL;DR: The physical chemistry of tau is crucial for governing its propensity for biomolecular condensation which is governed by various intermolecular and intramolecular interactions leading to simple one-component and complex multi-component condensates as mentioned in this paper.
Journal ArticleDOI
Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications.
Niccolò Candelise,Silvia Scaricamazza,Illari Salvatori,Alberto Ferri,Cristiana Valle,Valeria Manganelli,Tina Garofalo,Maurizio Sorice,Roberta Misasi +8 more
TL;DR: In this paper, a review of the heterogeneity of structures that are produced from intrinsically disordered protein domains and highlight the routes that lead to the formation of physiological liquid droplets as well as pathogenic aggregates is presented.
Journal ArticleDOI
Technological advances in super-resolution microscopy to study cellular processes
TL;DR: In this paper , the authors review the technical details behind the most common implementations of super-resolution microscopy and highlight some of the recent, promising advances in this field, and present a new window into visualizing the inner life of cells at unprecedented levels of detail.
Journal ArticleDOI
Mouse closed head traumatic brain injury replicates the histological tau pathology pattern of human disease: characterization of a novel model and systematic review of the literature.
Aydan Kahriman,James P. Bouley,Thomas W. Smith,Daryl A. Bosco,Amanda L. Woerman,Nils Henninger +5 more
TL;DR: In this article, the authors conducted longitudinal histopathological characterization of a mouse closed-head TBI model, with a focus on pathological features reported in human TBI-associated tauopathy.
References
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Proceedings Article
A density-based algorithm for discovering clusters in large spatial Databases with Noise
TL;DR: DBSCAN, a new clustering algorithm relying on a density-based notion of clusters which is designed to discover clusters of arbitrary shape, is presented which requires only one input parameter and supports the user in determining an appropriate value for it.
Journal ArticleDOI
Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology
Inge Grundke-Iqbal,Khalid Iqbal,Yunn-Chyn Tung,Maureen Quinlan,Henryk M. Wisniewski,Lester I. Binder +5 more
TL;DR: It is suggested that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF, the two major locations of paired-helical filaments in Alzheimer disease brain.
Journal ArticleDOI
Cryo-EM structures of tau filaments from Alzheimer’s disease
Anthony W. P. Fitzpatrick,Benjamin Falcon,Shaoda He,Alexey G. Murzin,Garib N. Murshudov,Holly J. Garringer,R. Anthony Crowther,Bernardino Ghetti,Michel Goedert,Sjors H.W. Scheres +9 more
TL;DR: Scheres et al. as mentioned in this paper presented a 3.4-3.5-resolution image of the brain of an individual with Alzheimer's disease and showed that the protein cores are made of two identical protofilaments comprising residues 306-378 of tau protein.
Journal ArticleDOI
Differential regulation of dynein and kinesin motor proteins by tau.
TL;DR: The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport.
Journal ArticleDOI
Tauopathy in Drosophila: Neurodegeneration Without Neurofibrillary Tangles
Curtis W. Wittmann,Matthew F. Wszolek,Joshua M. Shulman,Paul M. Salvaterra,Jada Lewis,Mike Hutton,Mel B. Feany +6 more
TL;DR: A genetic model of tau-related neurodegenerative disease is created by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila melanogaster to allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.