Publications associées à Single Posttranslational Modifications in the Central Repeat Domains of Tau4 Impact its Aggregation and Tubulin Binding

Tubulin engineering by semi-synthesis reveals that polyglutamylation directs detyrosination

Luc Reymond, Pierre Gönczy, Nora Guidotti, Beat Fierz, Ninad Dilip Agashe, Georgios Hatzopoulos, Timothy Matthias Reichart, Eduard Hubert Theodoor Marius Ebberink, Fabian Zacharias Schneider, Cédric Pourroy, Po-Han Chang

Microtubules, a critical component of the cytoskeleton, carry post-translational modifications (PTMs) that are important for the regulation of key cellular processes. Long-lived microtubules, in neurons particularly, exhibit both detyrosination of a-tubuli ...

NATURE PORTFOLIO2023

Capturing the heterogeneity of alpha-synuclein pathology in synucleinopathies

Melek Firat Altay

Synucleinopathies such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy (MSA) are detrimental neurodegenerative diseases. Alpha-synuclein (aSyn), the main aggregating protein found in the pathological inclusions of these ailmen ...

EPFL2022

Site-Specific Hyperphosphorylation Inhibits, Rather than Promotes, Tau Fibrillization, Seeding Capacity, and Its Microtubule Binding

Hilal Lashuel, Mahmood Haj Yahya, Gopinath Pushparathinam, Rajasekhar Kolla

The consistent observation of phosphorylated tau in the pathology of Alzheimer's disease has contributed to the emergence of a model where hyperphosphorylation triggers both tau disassociation from microtubules and its subsequent aggregation. Herein, we ap ...

Wiley-VCH Verlag GmbH2020

Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau

Hilal Lashuel, Anass Chiki, Nadine Aït Bouziad, Galina Limorenko

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's norma ...

2020

Anti-Aβ antibodies bound to neuritic plaques enhance microglia activity and mitigate tau pathology

Philippe Colin, Bernard Schneider, Vanessa Laversenne

The brain pathology of Alzheimer’s disease (AD) is characterized by the misfolding and aggregation of both the amyloid beta (Aβ) peptide and hyperphosphorylated forms of the tau protein. Initial Aβ deposition is considered to trigger a sequence of deleteri ...

2020

Centriole foci persist in starfish oocytes despite Polo-like kinase 1 inactivation or loss of microtubule nucleation activity

Pierre Gönczy, Marie Juliette Ségolène Pierron, Nils Kalbfuss

Centrioles must be eliminated or inactivated from the oocyte to ensure that only the two functional centrioles contributed by the sperm are present in the zygote. Such removal can occur during oogenesis, as in Drosophila, where departure of Polo kinase fro ...

2020

A method for preparing phfs-like tau aggregates

Hilal Lashuel, Nadine Aït Bouziad

The invention relates to a method for preparing PHFs-like Tau aggregates and to a method for identifying compounds that are inhibitors of Tau protein aggregation, blockers of Tau seeding and propagation, and imaging agents that specifically bind PHF. ...

2019

Protein Engineering Tools to Explore the Function of Protein Post-Translational Modifications for Chromatin and Microtubule Cytoskeletal Biology

Ninad Dilip Agashe

Protein post-translational modifications (PTMs) play a crucial role in expanding the protein diversity and are one of the major mechanisms through which cells respond to ever changing environmental cues. The function of two of the most important cellular c ...

EPFL2019

Application of anti-amyloid beta immunization using encapsulated cell technology in mouse models of Alzheimer's disease

Vanessa Laversenne

Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is characterized by the deposition of two aggregated proteins: Amyloid beta (Aß) and hyperphosphorylated tau. Accumulations of these proteins are thought to be the signature ...

EPFL2019

Flagellar microtubule doublet assembly in vitro reveals a regulatory role of tubulin C-terminal tails

Davide Demurtas, Virginie Hamel, Paul Guichard

Microtubule doublets (MTDs), consisting of an incomplete B-microtubule at the surface of a complete A-microtubule, provide a structural scaffold mediating intraflagellar transport and ciliary beating. Despite the fundamental role of MTDs, the molecular mec ...

American Association for the Advancement of Science2019

alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease

Hilal Lashuel, Anne-Laure Mahul Mellier

A compelling link is emerging between the posttranslational modification O-GlcNAc and protein aggregation. A prime example is alpha-synuclein, which forms toxic aggregates that are associated with neurodegeneration in Parkinson's and related diseases. alph ...

National Academy of Sciences2019

A viral vector based in vivo model of tauopathy to explore therapeutic strategies against tau pathology

Sameer Mohammad Khaleel Nazeeruddin

Tauopathies are neurodegenerative diseases whose common pathological feature is the intraneuronal accumulation of tau aggregates. Tau protein has various roles in the neuron, among which stabilization of microtubules (MT), regulation of synaptic activity o ...

EPFL2019

Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay

Hilal Lashuel, Sean Michael Deguire, Lara Petricca

Accumulation and aggregation of misfolded alpha-synuclein is believed to be a cause of Parkinson's disease (PD). Phosphorylation of alpha-synuclein at S129 is known to be associated with the pathological misfolding process, but efforts to investigate the r ...

2019

Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States

Hilal Lashuel, Mahmood Haj Yahya

The microtubule-associated protein Tau plays a central role in neurodegeneration and is a leading therapeutic target for the treatment of Alzheimer’s disease (AD). Several lines of evidence suggest that post-translational modifications (PTMs) regulate the ...

2018

Calpain-mediated tau fragmentation is altered in Alzheimer's disease progression

Andrea Pfeifer, Andreas Muhs

The aggregation of intracellular tau protein is a major hallmark of Alzheimer's disease (AD). The extent and the stereotypical spread of tau pathology in the AD brain are correlated with cognitive decline during disease progression. Here we present an in-d ...

Nature Research2018

Sequence and structural determinants of Tau aggregation and seeding capacity: Implications for Neurofibrillary Tangle formation and Tau toxicity in Alzheimer's disease

Nadine Aït Bouziad

Despite decades of research in Alzheimerâ s disease (AD), no treatment has been found to efficiently prevent or cure its progression. The microtubule binding protein Tau plays central roles in the pathogenesis of AD and is found, in the form of paired hel ...

EPFL2017

Discovery and characterization of novel stable tau oligomeric complexes: Implications for the role of Tau/phospholipid interactions in regulating its functions in health and disease

Hilal Lashuel, Nadine Aït Bouziad, Gizem Zorludemir, Anne-Laure Mahul Mellier

The microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer's disease. Although Tau interaction with membranes is thought to affect some of its physiological functions and its aggregation properties, the sequence determinan ...

Nature Publishing Group2017

Microtubule-Binding R3 Fragment from Tau Self-Assembles into Giant Multistranded Amyloid Ribbons

Raffaele Mezzenga, Hilal Lashuel, Nadine Aït Bouziad

Tau protein and its fragments self-assemble into amyloid fibrils in the presence of polyanions, such as heparin. By combining microscopy, scattering, and spectroscopy techniques, we studied the aggregation of the 26-mer Tau-derived peptide alone, Tau306-32 ...

Wiley-VCH Verlag GmbH2016

The Human Centriolar Protein CEP135 Contains a Two-Stranded Coiled-Coil Domain Critical for Microtubule Binding

Pierre Gönczy, Paul Guichard, Georgios Hatzopoulos

Centrioles are microtubule-based structures that play important roles notably in cell division and cilium biogenesis. CEP135/Bld10p family members are evolutionarily conserved microtubule-binding proteins important for centriole formation. Here, we analyze ...

Elsevier2016

How many lives does CLIMP-63 have?

Françoise Gisou van der Goot Grunberg, Patrick Alain Sandoz

In 1995, in the Biochemical Society Transactions, Mundy published the first review on CLIMP-63 (cytoskeletonlinking membrane protein 63) or CKPA4 (cytoskeleton-associated protein 4), initially just p63 [1]. Here we review the following 20 years of research ...

2015