A5078313558- Drug Transport and Resistance Mechanisms
- Pediatric Hepatobiliary Diseases and Treatments
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Cancer Research and Treatments
- Escherichia coli research studies
- Nanoparticle-Based Drug Delivery
- Virus-based gene therapy research
- Cystic Fibrosis Research Advances
- Bacteriophages and microbial interactions
- Calcium signaling and nucleotide metabolism
- Cholesterol and Lipid Metabolism
- Advanced biosensing and bioanalysis techniques
- Neonatal Health and Biochemistry
- Liver Diseases and Immunity
- Viral gastroenteritis research and epidemiology
- RNA Interference and Gene Delivery
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Inflammatory Bowel Disease
- Iron Metabolism and Disorders
- Toxin Mechanisms and Immunotoxins
- Microtubule and mitosis dynamics
- Pharmacological Effects and Toxicity Studies
- Trace Elements in Health
Inserm
2014-2025
Université Paris-Saclay
2020-2024
Physiopathogénèse et Traitement des Maladies du Foie
2021-2024
Institut Curie
2001-2023
Centre National de la Recherche Scientifique
2005-2023
Physiopathologie et Epidémiologie des Maladies Respiratoires
2021
Sorbonne Université
2013-2019
Centre de Recherche Saint-Antoine
2013-2019
Fondation pour l’innovation en Cadiométabolisme et Nutrition
2014
University of Geneva
2006-2011
In HeLa cells, Shiga toxin B-subunit is transported from the plasma membrane to endoplasmic reticulum, via early endosomes and Golgi apparatus, circumventing late endocytic pathway. We describe here that in cells derived human monocytes, i.e., macrophages dendritic was internalized a receptor-dependent manner, but retrograde transport biosynthetic/secretory pathway did not occur part of protein degraded lysosomes. These differences correlated with observation associated Triton...
Progressive familial intrahepatic cholestasis type 3 is caused by biallelic variations of ABCB4, most often (≥70%) missense. In this study, we examined the effects 12 missense identified in progressive patients. We classified these on basis defects thus and explored potential rescue trafficking‐defective mutants pharmacological means. Variations were reproduced ABCB4 complementary DNA mutants, obtained, expressed HepG2 HEK293 cells. Three either fully (I541F L556R) or largely (Q855L)...
The closely related Rab6 isoforms, Rab6A and Rab6A′, have been shown to regulate vesicular trafficking within the Golgi post‐Golgi compartments, but studies using dominant active or negative mutant suggested conflicting models. Here, we report that reduction in expression of isoform specific small interfering RNA reveals noticeable differences Rab6A′ biological functions. Surprisingly, seems be largely dispensable membrane events, whereas knocking down hampers intracellular transport...
Retrograde transport allows proteins and lipids to leave the endocytic pathway reach other intracellular compartments, such as trans-Golgi network (TGN)/Golgi membranes, endoplasmic reticulum and, in some instances, cytosol. Here, we have used RNA interference against SNARE syntaxin 5 16, combined with recently developed quantitative trafficking assays, morphological approaches cell intoxication analysis show that these are not only required for efficient retrograde of Shiga toxin, but also...
Endosomes along the degradation pathway leading to lysosomes accumulate membranes in their lumen and thus exhibit a characteristic multivesicular appearance. These lumenal typically incorporate down-regulated EGF receptor destined for degradation, but mechanisms that control formation remain poorly characterized. Here, we describe novel quantitative biochemical assay reconstitutes of vesicles within late endosomes vitro. Vesicle budding into endosome was time-, temperature-, pH-,...
Receptor-mediated internalization to the endoplasmic reticulum (ER) and subsequent retro-translocation cytosol are essential sequential processes required for productive intoxication of susceptible mammalian cells by Shiga-like toxin-1 (SLTx). Recently, it has been proposed that observed association certain ER-directed toxins viruses with detergent-resistant membranes (DRM) may provide a general mechanism their retrograde transport (ER). Here, we show DRM recruitment SLTx bound its...
Abstract The targeting of solid tumors requires delivery tools that resist intracellular and extracellular inactivation, are taken up specifically by tumor cells. We have shown previously the recombinant nontoxic B-subunit Shiga toxin (STxB) can serve as a tool to target digestive in animal models. aim this study was expand these experiments human colorectal cancer. Tissue samples normal colon, benign adenomas, carcinomas, liver metastases from 111 patients were obtained for quantification...
Abstract Efficient methods for tumor targeting are eagerly awaited and must satisfy several challenges: molecular specificity, transport through physiologic barriers, capacity to withstand extracellular or intracellular degradation inactivation by the immune system. Through interaction with its hosts, intestinal pathogen-produced Shiga toxin has evolved properties that of interest in this context. Its nontoxic B-subunit binds cellular receptor, glycosphingolipid Gb3, which is highly...
Alterations in apical junctional complexes (AJCs) have been reported genetic or acquired biliary diseases. The vitamin D nuclear receptor (VDR), predominantly expressed epithelial cells the liver, has shown to regulate AJCs. aim of our study was thus investigate role VDR maintenance bile duct integrity mice challenged with biliary-type liver injury. Vdr(-/-) subjected ligation (BDL) displayed increased damage compared wildtype BDL mice. Adaptation cholestasis, ascertained by expression genes...
The ABCB4 transporter mediates phosphatidylcholine (PC) secretion at the canalicular membrane of hepatocytes and its genetic defects cause biliary diseases. Whereas shares high sequence identity with multidrug transporter, ABCB1, N-terminal domain is poorly conserved, leading us to hypothesize a functional specificity this domain. A database genotyping in large series patients was screened for variations altering residues Identified variants were then expressed cell models investigate their...
The canalicular bile salt export pump (BSEP/ABCB11) of hepatocytes is the main adenosine triphosphate (ATP)-binding cassette (ABC) transporter responsible for acid secretion. Mutations in ABCB11 cause several cholestatic diseases, including progressive familial intrahepatic cholestasis type 2 (PFIC2) often lethal absence liver transplantation. We investigated vitro effect and potential rescue a BSEP mutation by ivacaftor, clinically approved cystic fibrosis transmembrane conductance...
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disease caused by biallelic variations in ABCB4. Data reporting on the impact of genotype and response to ursodeoxycholic acid (UDCA) therapy long-term outcomes are scarce.We retrospectively describe cohort 38 patients with PFIC3 median age at last follow-up 19.5 years (range 3.8-53.8).Twenty presented symptoms before 1 year age. Thirty-one received resulting serum test improvement 20. Twenty-seven had cirrhosis 8.1...
ABCB4 is an ATP-binding cassette transporter expressed at the canalicular membrane of hepatocytes and responsible for translocating phosphatidylcholine into bile. Despite recent cryo-EM structures ABCB4, knowledge about molecular mechanism transport remains fragmented. In this study, we used all-atom dynamics simulations to investigate during its cycle, leveraging both symmetric asymmetric models. Our results demonstrate that composition influences local conformational revealing distinct...
Globotriasosylceramide (Gb3), a neutral glycosphingolipid, is the B-cell differentiation antigen CD77 and acts as receptor for most Shiga toxins, including verotoxin-1 (VT-1). We have shown that both anti-Gb3/CD77 mAb VT-1 induce apoptosis in Burkitt's lymphoma cells. compared apoptotic pathways induced by these two molecules selecting cell lines sensitive to only one of inducers or both. In all (including apoptosis-resistant line), was transported endoplasmic reticulum inhibited protein...
Like other enveloped viruses, vesicular stomatitis virus infects cells through endosomes. There, the viral envelope undergoes fusion with endosomal membranes, thereby releasing nucleocapsid into cytoplasm and allowing infection to proceed. Previously, we reported that fuses preferentially membrane of vesicles present within multivesicular Then, these intra-endosomal (containing nucleocapsids) are transported late endosomes, where back-fusion endosome limiting delivers cytoplasm. In this...
Many studies have investigated the intracellular trafficking of Shiga toxin, but very little is known about underlying dynamics its cellular receptor, glycosphingolipid globotriaosyl ceramide. In this study, we show that ceramide required not only for toxin binding to cells, also trafficking. induces recruitment detergent‐resistant membranes, and subsequent internalization lipid. The pool at plasma membrane then replenished from internal stores. Whereas endocytosis affected in recovery...
The biogenesis of multivesicular endosomes and the sorting activated signaling receptors into depend on soluble protein complexes (ESCRT complexes), which transiently interact with receptor cargo endosomal membrane. Previously, it was shown that transmembrane secretory carrier membrane (SCAMP) 3, is present endosomes, interacts ESCRT components. Here, we report SCAMP3 plays a role in endosomes. We find EGF formation intralumenal vesicles within these vitro thus also controls targeting to...
In many cell lines, such as HeLa cells, STxB (Shiga toxin B-subunit) is transported from the plasma membrane to ER (endoplasmic reticulum), via early/recycling endosomes and Golgi apparatus, bypassing late endocytic pathway. human monocyte-derived macrophages dendritic cells that are not sensitive Shiga toxin-induced protein biosynthesis inhibition, detectably targeted retrograde route degraded in endosomes/lysosomes.We have identified B-subunit interacting proteins macrophages. ER-localized...
Abstract Adenosine triphosphate binding cassette transporter, subfamily B member 4 (ABCB4) is the transporter of phosphatidylcholine at canalicular membrane hepatocytes. ABCB4 deficiency, due to genetic variations, responsible for progressive familial intrahepatic cholestasis type 3 (PFIC3) and other rare biliary diseases. Roscovitine a molecule in clinical trial that was shown correct F508del variant cystic fibrosis transmembrane conductance regulator (CFTR), another ABC transporter. In...