Publications associées à Tubulin engineering by semi-synthesis reveals that polyglutamylation directs detyrosination

Microtubule-mediated GLUT4 trafficking is disrupted in insulin-resistant skeletal muscle

Martinus Gijs, Raphaël Etienne Jean Trouillon, Martin Rainer Wohlwend

Microtubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based ...

eLIFE SCIENCES PUBL LTD2023

Structures of SAS-6 coiled coil hold implications for the polarity of the centriolar cartwheel

Pierre Gönczy, Georgios Hatzopoulos

Centrioles are eukaryotic organelles that template the formation of cilia and flagella, as well as organize the microtubule network and the mitotic spindle in animal cells. Centrioles have proximal-distal polarity and a 9 fold radial symmetry imparted by a ...

CELL PRESS2022

Applying Peptide and Protein Synthesis to Study Post-translational Modifications in Epigenetics and Beyond

Beat Fierz

Epigenetics research focuses on the study of heritable gene regulatory mechanisms that do not involve changes of the DNA sequence. Such mechanisms include post-translational modifications of histone proteins that organize the genome in the nucleus into a n ...

2021

A helical inner scaffold provides a structural basis for centriole cohesion

Henning Paul-Julius Stahlberg, Virginie Hamel, Paul Guichard, Davide Gambarotto

The ninefold radial arrangement of microtubule triplets (MTTs) is the hallmark of the centriole, a conserved organelle crucial for the formation of centrosomes and cilia. Although strong cohesion between MTTs is critical to resist forces applied by ciliary ...

2020

Wnt-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitosis in zebrafish

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami

Oriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divi ...

Nature Publishing Group2020

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

Development of chemical biology tools to reveal the function and organization of the silenced chromatin state

Nora Guidotti

Effector proteins are recruited to chromatin via transient interactions between their reader domains and histone post-translational modification (PTM) patterns. These interactions form signaling pathways that control gene expression or repression and which ...

EPFL2020

Observing protein interaction dynamics to chemically defined chromatin fibers by colocalization single-molecule fluorescence microscopy

Maxime Nicolas Mivelaz, Beat Fierz

In eukaryotic cells, the genome is packaged into chromatin and exists in different states, ranging from open euchromatic regions to highly condensed heterochromatic regions. Chromatin states are highly dynamic and are organized by an interplay of histone p ...

2020

The role of histone tails in nucleosome stability: An electrostatic perspective

Alessandro Samuele Patelli

We propose a methodology for the study of protein-DNA electrostatic interactions and apply it to clarify the effect of histone tails in nucleosomes. This method can be used to correlate electrostatic interactions to structural and functional features of pr ...

2020

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

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

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

Hilal Lashuel, Mahmood Haj Yahya

A variety of methods have been employed to study the impact of posttranslational modifications on Tau protein function. Here, a semisynthesis strategy is described that enables selective modification within the central repeat domain of Tau4 (residues 291-3 ...

Wiley-VCH Verlag GmbH2019

A bi-terminal protein ligation strategy to probe chromatin structure during DNA damage

Beat Fierz, Sinan Kilic, Carolin Christine Lechner, Iuliia Boichenko

The cellular response to DNA damage results in a signaling cascade that primes chromatin for repair. Combinatorial post-translational modifications (PTMs) play a key role in this process by altering the physical properties of chromatin and recruiting downs ...

2018

Dynamic protein-chromatin interactions in heterochromatin and during the DNA damage response on the single molecule level

Andreas Linus Bachmann

Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable he ...

EPFL2018

Genetically encoded multivalent sensors to detect bivalent epigenetic modifications in living stem cells

Aurore Marie-France Delachat

Eukaryotic DNA is organized in the form of chromatin whose basic unit is the nucleosome. The four core histones forming the nucleosome, H2A, H2B, H3 and H4 can be highly post-translationally modified, especially on their N-terminal tail protruding from the ...

EPFL2017

Chemical Genetic Screen Identifies Natural Products that Modulate Centriole Number

Kai Johnsson, Pierre Gönczy, Zhou Fang, Michele Graciotti

Centrioles are microtubule-based organelles found in most eukaryotic cells and that are critical for the formation of cilia and flagella, as well as of centrosomes in animal cells. The number of centrioles must be strictly regulated in proliferating cells ...

Wiley-Blackwell2016

Acetylated tubulin is essential for touch sensation in mice

Kai Johnsson, Luc Reymond, Antonino Asaro

At its most fundamental level, touch sensation requires the translation of mechanical energy into mechanosensitive ion channel opening, thereby generating electro-chemical signals. Our understanding of this process, especially how the cytoskeleton influenc ...

Elife Sciences Publications Ltd2016

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

SAS-1 Is a C2 Domain Protein Critical for Centriole Integrity in C. elegans

Simon Blanchoud, Graham Knott, Pierre Gönczy, Tamara Mikeladze-Dvali, Lukas von Tobel

Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sp ...

Public Library of Science2014

Mechanisms of LRRK2-Mediated Neurodegeneration

Darren Moore, Elpida Tsika

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of familial Parkinson's disease (PD), whereas common variation at the LRRK2 locus is associated with an increased risk of idiopathic PD. Considerable progress has be ...

Current Science Inc., Springer2012