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Les événements du mois


  • Biologie Cellulaire

    • Friday 22 September 11:00-12:30 - Vesa Markus OLKKONEN - Minerva Foundation Institute for Medical Research, Helsingfors, Finlande, invité par Francesca Giordano

      OSBP-related protein 2 (ORP2): A new regulatory node between cellular energy metabolism, adhesion, migration and proliferation

      Résumé : ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in triacylglycerol (TG) metabolism at endoplasmic reticulum (ER) - lipid droplet (LD) contacts, cholesterol transport, and adrenocortical steroidogenesis. We now characterize the functional role of ORP2 by employing ORP2-knock-out (KO) hepatoma cells generated by CRISPR-Cas9 gene editing. Loss of ORP2 did not affect the major cellular phospholipids, cholesterol, or oxysterols, nor the quantity of ER-LD contact sites. However, the knock-out resulted in reduced expression of SREBP-1 target genes and mRNAs encoding glycolytic enzymes, defective TG synthesis and storage, inhibition of LD growth upon fatty acid loading, reduction of glucose uptake, glycogen synthesis, glycolysis (ECAR) and Akt activity. ORP2 was found to form a physical complex with key controllers of Akt, Cdc37 and Hsp90. In addition to the metabolic phenotypes, the ORP2-KO cells showed defects in adhesion, lamellipodieae formation, migration and proliferation, and the ORP2 interactome contained, in addition to Cdc37, a number of actin regulatory components. The putative lipid transport steps that ORP2 function may involve are as yet unknown, albeit we find a sterol-PI4P countertransport function quite possible.
      To conclude, the present study identifies ORP2 as new regulatory node between cellular energy metabolism, adhesion, migration and proliferation.

      Lieu : Bibliothèque - bâtiment 34 - Campus de Gif-sur-yvette


    • Friday 6 October 11:00-12:30 - Yvon JAILLAIS - ENS LYON, invité par Grégory Vert

      Séminaire Yvon JAILLAIS

      Lieu : Auditorium - bâtiment 21 - Campus de Gif-sur-yvette


  • I2BC

    • Friday 13 October 14:00-15:00 - Dr Felipe Cava - Department of Molecular Biology, Umeå University, Suède

      Your I2BC Seminar : The MUREINome: Defining the fundamental principles that govern bacterial cell wall homeostasis

      Lieu : Auditorium - Bâtiment 21, campus de Gif


  • Virologie

    • Monday 2 October 11:00-12:00 - Dr Arnaud Morris - Centre d'Immunologie et des Maladies Infectieuses, La Pitié Salpêtrière, Paris

      Learning from viruses to dissect the cell biology of antigen presentation

      Résumé : The work of our team is at the interface between cellular biology, virology and immunology. We characterize the interactions between viruses and immune cells with a focus on viral antigen presentation by infected cells to T lymphocytes. Our aim is to identify novel sources of viral antigens and to define unconventional cellular pathways involved in antigen processing that influence the activation of T lymphocytes. During this presentation, I will highlight the diversity of antigens that are encoded by virally infected cells, in particular the usage of alternative reading frames as a source of antigenic peptides. I will also present on going work on protein-adaptor, involved in autophagy, and their role in antigen degradation and T cell activation.

      Lieu : Salle de séminaires - Bâtiment 14, campus de gif


  • Microbiologie

    • Tuesday 3 October 11:30-12:30 - Dr Alexandre Chenal - Groupe BiophysiCyaA Laboratoire de Biochimie des Intéractions Macromoléculaires Département de Biologie Structurale et Chimie Institut Pasteur, Paris

      Bordetella pertussis CyaA toxin: secretion, folding, translocation and host cell hijacking

      Résumé : The adenylate cyclase toxin (CyaA, 1706 residues) is an RTX protein that plays an essential role in the early stages of respiratory tract colonization by Bordetella pertussis, the causative agent of whooping cough. Its cell intoxication process, however, is still poorly understood. After its secretion through a dedicated type 1 secretion system, CyaA intoxicates human cells via a unique mechanism of translocation of its catalytic domain (AC) directly across the plasma membrane of target cells. Once in the cytosol, AC interacts with calmodulin (CaM) and produces supraphysiological levels of cAMP, leading to cell death. I will present some recent data, which covers several steps of this intoxication process. Our results illustrate the structural flexibility of bacterial toxins adapted to various functions and contexts, such as toxin secretion and refolding, AC translocation, and enzymatic AC:CaM complex formation. Our data further shows the adaptation of bacterial RTX toxins to the diverse array of calcium concentrations encountered in the successive environments during the intoxication process. Finally, due to its hydrophobic character, CyaA is known for its propensity to aggregate into multimeric forms in the absence of a chaotropic agent in vitro. We have recently defined the experimental conditions required for CyaA folding into a stable, monomeric and functional form. This opens new perspectives for both basic science and CyaA-based biotechnological applications developed in the lab, i.e., to improve antigen delivery vehicles and new pertussis vaccines.

      Lieu : Salle A. Kalogeropoulos - Bâtiment 400, campus d’Orsay


  • B3S

    • Thursday 21 September 15:30-16:30 - Pr Shunichi Takeda - Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

      The role Mre11-Rad50-Nbs1 complex in double-strand-break repair – Myth and Facts

      Résumé : Homologous recombination initiates double-strand break (DSB) repair by digesting 5’-termini at DSBs, the biochemical reaction called DSB resection, during which DSBs are processed by nucleases to generate 3’ single-strand DNA. Rad51 recombinase polymerizes along resected DNA, and resulting Rad51-DNA complex undergoes homology search. Although DSB resection by the Mre11 nuclease plays a critical role in HR in Saccharomyces cerevisiae, it remains elusive whether DSB resection by Mre11 significantly contributes to HR-dependent DSB repair in mammalian cells. Depletion of Mre11 decreases the efficiency of DSB resection only by a few times in mammalian cells. We show that although Mre11 is required for efficient HR-dependent repair of ionizing-radiation-induced DSBs, Mre11 is largely dispensable for DSB resection in both chicken DT40 and human TK6 B cell lines. Moreover, 2- to 3-fold decrease in DSB resection has virtually no impact on the efficiency of HR. Thus, although a large number of literatures have reported the vital role of Mre11-mediated DSB resection in HR, the role may not explain the very severe defect in HR in Mre11-deficient cells including their lethality. We here show experimental evidences for the additional roles of Mre11 in (i) elimination of chemical adducts from DSB ends for subsequent DSB repair, and (ii) maintaining homologous recombination intermediates for their proper resolution.
      Contact : Jean-Baptiste Charbonnier

      Lieu : Salle de Conférences - Bâtiment 144, Campus de Saclay


  • cytoskeleton club

    • Tuesday 10 October 11:30-12:30 -

      Cytoskeleton club

      Lieu : Bibliothèque - bâtiment 34, campus de Gif



  • B3S

    • Monday 16 October 14:00-17:00 - The Quyen Nguyen - team : Structural Biochemistry of Microtubules, Kinesins and their Cargos

      Structural characterization of JIP1 recruitment by kinesin1 light chain (KLC)

      Résumé : Kinesins are molecular motors involved in the intracellular transport of many cargos within the cell. Although the motility of kinesins is well understood, the molecular mechanisms underlying cargo recruitment are much less so. Kinesin1 plays various roles in neuronal cells, where it contributes to the spatial and temporal organization of many cellular components. It would play a role in various neurological pathologies, such as Alzheimer’s disease. Understanding how kinesin1 recognizes and interacts with its cargos is important to decorticate its role, as well as that of its cargos, in normal and pathological cells. Kinesin1 is a heterotetramer consisting of two heavy chains (KHC) and two light chains (KLC), both of which are capable of recruiting cargo proteins. One of the first cargo proteins to have been identified is JNK-interacting protein 1 (JIP1) which is: (i) a scaffold protein for the signaling pathway of MAP kinases and (ii) an adaptor protein for transporting amyloid precursor protein (APP) responsible for Alzheimer’s disease. In both cases, JIP1 regulates critical processes at the cell level, making it an interesting protein to study. Early studies have led to a better understanding of how JIP1 is recruited and transported by kinesin1. However, the detail of the interaction between KLC and JIP1 is not yet fully described and therefore understood.
      Objectives: My doctoral work aims at characterizing at the molecular level the interaction between KLC and JIP1. To do this, I had the following objectives: 1) to characterize the interaction domains of the two proteins alone, 2) to study the formation of the complex in solution by biophysical approaches, and 3) to determine the 3D structure of the complex by crystallography.
      Results: Initially, I characterized the TPR domain of KLC alone, contributing among others to the development of a molecular toolbox. I also participated in the determination of two crystallographic structures of the TPR domain of KLC1/2 that highlights the structural plasticity of the first helix of this domain (Nguyen et al, submitted). In a second step, I set up the conditions for the expression and purification of the PTB domain of JIP1 and carry out the structural characterization of this domain in solution. Although this domain of JIP1 is not necessary for interaction with KLC, I studied the impact of its presence on recruitment by KLC. Finally, I characterized the recruitment of JIP1 by KLC by confirming a number of information on the interaction between the KLC-TPR and the C-terminal region (Cter) of JIP1 at the molecular level. The numerous crystallization tests that I carried out did not make it possible to obtain crystals of the KLC: JIP1 complex. However, I was able to precisely map the interaction zone of JIP1-Cter with the KLC-TPR domain using the various KLC tools available by determining by ITC their affinity with JIP1-Cter (Nguyen et al., In preparation).
      Conclusion: Thus, my PhD work allowed to better understand 1) the structural versatility of the KLC-TPR domain, 2) the impact of the JIP1-PTB domain for its KLC recruitment, and 3) the interaction mode of JIP1 by KLC.
      Keywords : Kinesin1, KLC-TPR, JIP1
      Co-responsables : Paola Llinas et Julie Ménétrey

      Lieu : Bibliothèque - Bâtiment 34, Campus de Gif


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