A5076325070- Lipid Membrane Structure and Behavior
- Bacillus and Francisella bacterial research
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Bacterial Genetics and Biotechnology
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- ATP Synthase and ATPases Research
- Inflammasome and immune disorders
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Caveolin-1 and cellular processes
- Nanopore and Nanochannel Transport Studies
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Poxvirus research and outbreaks
- Cancer-related gene regulation
- Streptococcal Infections and Treatments
- Bacteriophages and microbial interactions
- Wnt/β-catenin signaling in development and cancer
École Polytechnique Fédérale de Lausanne
2015-2024
Weatherford College
2023
University of Geneva
1998-2023
Université Laval
2004
The University of Queensland
1998
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
1994-1998
CEA Paris-Saclay
1994-1998
Laboratoire de Neurobiologie Cellulaire et Moléculaire
1994-1996
The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) be taken up exert its toxic effect in cytoplasm. Here, we report that clustering (ATR) with heptameric PA or an antibody sandwich causes association specialized cholesterol glycosphingolipid-rich microdomains plasma membrane (lipid rafts). We find although endocytosis ATR is slow, it into rafts either via heptamerization using necessary sufficient trigger efficient...
Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein remain largely unexplored. Recent developments new chemical methods have allowed establishment palmitoyl-proteomes variety cell lines tissues from different species. As amount information generated by these high-throughput studies increasing, field requires centralization comparison this information. Here we present SwissPalm...
SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found during infection, spike becomes modified, through the sequential action of S-acyltransferases ZDHHC20 9. Particularly striking is rapid acylation on 10 cytosolic cysteines within ER Golgi. Using combination computational, lipidomics, biochemical approaches, we show this massive lipidation controls biogenesis degradation, drives...
Cytolytic pore-forming toxins are important for the virulence of many disease-causing bacteria. How target cells molecularly respond to these and whether or not they can mount a defense poorly understood. By using microarrays, we demonstrate that nematode Caenorhabditis elegans responds robustly Cry5B, member Crystal toxin family made by Bacillus thuringiensis . This genomic response is distinct from seen with different stressor, heavy metal cadmium. A p38 mitogen-activated protein kinase...
In this paper, we have investigated the effects of pore-forming toxin aerolysin, produced by Aeromonas hydrophila, on mammalian cells. Our data indicate that protoxin binds to an 80-kD glycosyl-phosphatidylinositol (GPI)-anchored protein BHK cells, and bound is associated with specialized plasma membrane domains, described as detergent-insoluble microdomains, or cholesterol-glycolipid “rafts.” We show then processed its mature form host cell proteases. propose preferential association rafts,...
The protective antigen (PA) of anthrax toxin binds to a cell surface receptor, undergoes heptamerization, and the enzymatic subunits, lethal factor (LF) edema (EF). resulting complex is then endocytosed. Via mechanisms that depend on vacuolar ATPase require membrane insertion PA, LF EF are ultimately delivered cytoplasm where their targets reside. Here, we show PA already occurs in early endosomes, possibly only multivesicular regions, but subsequent delivery preferentially later endocytic...
The anthrax toxin is composed of three independent polypeptide chains. Successful intoxication only occurs when heptamerization the receptor-binding polypeptide, protective antigen (PA), allows binding two enzymatic subunits before endocytosis. We show that this tailored behavior caused by counteracting posttranslational modifications in cytoplasmic tail PA receptors. receptor palmitoylated, and unexpectedly prevents its association with lipid rafts and, thus, premature ubiquitination. This...
Anthrax lethal toxin is a classical AB comprised of two components: protective antigen (PA) and factor (LF). Here, we show that following assembly endocytosis, PA forms channel translocates LF, not only into the cytosol, but also lumen endosomal intraluminal vesicles (ILVs). These ILVs can fuse release LF where proteolyze disable host targets. We find persist in for days, fully sheltered from proteolytic degradation, both vitro vivo. During this time, ILV-localized be transmitted to daughter...
Canonical Wnt signaling is initiated by binding of proteins to members the Frizzled family and subsequent complex formation with lipoprotein receptor-related 5/6 (LRP5/6). Here, we show that LRP6 palmitoylated on a juxtamembranous cysteine palmitoylation required for exit from endoplasmic reticulum (ER). We propose serves tilt long, 23-residue transmembrane domain respect plane membrane prevent hydrophobic mismatch recognition ER quality control. In support this model,...
S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about DHHC palmitoyltransferase family still limited. Here we show that human ZDHHC6, which modifies key proteins of endoplasmic reticulum, controlled by an upstream palmitoyltransferase, ZDHHC16, revealing first palmitoylation cascade. The combination site specific mutagenesis three ZDHHC6 sites, experimental determination kinetic parameters and data-driven mathematical modelling allowed us to obtain...
The membrane of human immunodeficiency virus type 1 (HIV-1) virions contains high levels cholesterol and sphingomyelin, an enrichment that is explained by the preferential budding through raft microdomains plasma membrane. Upon depletion from HIV-1 with methyl-beta-cyclodextrin, infectivity was almost completely abolished. In contrast, this treatment had only a mild effect on infectiousness particles pseudotyped G envelope vesicular stomatitis virus. cholesterol-chelating compound nystatin...
It has been proposed that the plasma membrane of many cell types contains cholesterol-sphingolipid–rich microdomains. Here, we analyze role these microdomains in promoting oligomerization bacterial pore-forming toxin aerolysin. Aeroly-sin binds to cells, via glycosyl phosphatidylinositol- anchored receptors, as a hydrophilic soluble protein must polymerize into an amphipathic ring-like complex form pore. We first show can occur at >105-fold lower concentration surface living cells...
Aerolysin is secreted as an inactive dimeric precursor by the bacterium <i>Aeromonas hydrophila</i>. Proteolytic cleavage within a mobile loop near C terminus of protoxin required for oligomerization and channel formation. This contains sequence KVRRAR<sup>432</sup>, which should be recognized mammalian proprotein convertases such furin, PACE4, PC5/6A. Here we show that these three proteases cleave proaerolysin after Arg-432 <i>in vitro</i>, yielding active toxin. We also investigated...
The anthrax toxin is a tripartite toxin, where the two enzymatic subunits require third subunit, protective antigen (PA), to interact with cells and be escorted their cytoplasmic targets. PA binds via one of receptors, TEM8 CMG2. Interestingly, times triggers its own endocytosis, in particular through heptamerization PA. Here we show that ubiquitination receptors beta-arrestin-dependent manner this step required for clathrin-mediated endocytosis. In addition, find endocytosis dependent on...
Loss-of-function mutations in capillary morphogenesis gene 2 (CMG2/ANTXR2), a transmembrane surface protein, cause hyaline fibromatosis syndrome (HFS), severe genetic disorder that is characterized by large subcutaneous nodules, gingival hypertrophy and painful joint contracture. Here we show CMG2 an important regulator of collagen VI homoeostasis. loss function promotes accumulation patients, leading particular to nodule formation. Similarly, accumulates massively uteri Antxr2-/- mice,...
Hepatitis E virus (HEV) is a positive-strand RNA encoding 3 open reading frames (ORF). HEV ORF3 protein small, hitherto poorly characterized involved in viral particle secretion and possibly other functions. Here, we show that forms membrane-associated oligomers. Immunoblot analyses of expressed cell-free vs. cellular systems suggested posttranslational modification. Further revealed palmitoylated at cysteine residues its N-terminal region, as corroborated by 3H-palmitate labeling, the...
Peripheral membrane proteins (PMPs) associate with cellular membranes through post-translational modifications like S-palmitoylation. The Golgi apparatus is generally viewed as the transitory station where palmitoyl acyltransferases (PATs) modify PMPs, which are then transported to their ultimate destinations such plasma (PM). However, little substrate specificity among many PATs has been determined. Here we describe inherent partitioning of Gαo - α-subunit heterotrimeric Go PM and Golgi,...