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IPBS Seminar series - B. Antonny & T. Soldati



Bruno Antonny

Institut de Pharmacologie Moléculaire et Cellulaire, CNRS & Université Côte d’Azur, Valbonne, France

Molecular mechanism of cholesterol transfer by OSBP at membrane contact sites

The network of proteins that orchestrate the exquisite distribution of cholesterol among cellular organelles is not fully characterized. Here I will present recent molecular and cellular studies on Oxysterol-Binding Protein (OSBP), which drives cholesterol/PI4P exchange at contact sites between the endoplasmic reticulum (ER) and the trans Golgi network (TGN). Reconstitution experiments of lipid transfer shows that OSBP is capable of both bridging two membranes through its N-terminal half, and of transferring lipids between them through its C-terminal domain. The directionality of lipid transfer is imposed by PI4P, which is synthesised at the TGN and hydrolysed at the ER. Pharmacological targeting of OSBP and PI4P kinases in cultured cells with specific inhibitors indicate that OSBP is responsible for the export of most cholesterol from the ER and, for this, consumes about 50% of the amount of PI4P present in the cell. The dynamics of OSBP at membrane contact sites is secured by an N-terminal intrinsically unfolded region, which prevents OSBP from over accumulating in these regions. Because other lipid transfer proteins share with OSBP a similar domain organisation, the model of lipid transfer by OSBP might be quite general.

Selected references

  • Antonny et al. 2018 The Oxysterol-binding protein cycle: burning off PI(4)P to transport cholesterol. Annu Rev Biochem
  • Mesmin et al. 2017 Sterol transfer, PI4P consumption, and control of membrane lipid order by endogenous OSBP. EMBO J
  • Mesmin et al. 2013 A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell



Thierry Soldati

Department of Biochemistry - Faculty of Science - University of Geneva

Dictyostelium as a versatile host model to study conserved mechanisms of cell-autonomous immunity 

The first line of defence against bacterial infections are phagocytic cells of the innate immune system. While multicellular organisms use phagocytosis to kill microbes and initiate a sustained immune response, phagocytic amoebae internalise bacteria as nutrients, via mechanisms of recognition, signalling and killing that are surprisingly conserved. Dictyostelium is a social amoeba that feeds by phagocytosis and has a rudimentary but highly conserved cell-intrinsic immune system. It is genetically and biochemically tractable and has emerged as a powerful and experimentally versatile host model organism. Tuberculosis is a major threat for human health. Its causative agent, Mycobacterium tuberculosis, is a bacterium that infects alveolar macrophages and subverts their bactericidal pathways that normally protect the lungs from infection. Important aspects of mycobacteria pathogenicity and host defences during infection remain to be explored. We study the mechanisms of infection by Mycobacterium marinum, a close cousin of M. tuberculosis, which uses similar virulence strategies to re-program and proliferate inside macrophages. In particular, we use this Dictyostelium/M. marinum model to study the inter-relationships between host and pathogen in terms of nutritional immunity, acquisition of metabolites, interference with the membrane trafficking and cytsokeletal processes.  Recently, we have strongly focused on the pathways responding and repairing bacteria-mediated membrane damages, manipulation of autophagy and acquisition of lipids from the host.

Selected references

  • Trofimov et al. 2018 Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets. Sci Rep
  • Cardenal-Muñoz et al. 2018 When Dicty met Myco, a (not so) romantic story about one amoeba and its intracellular pathogen. Front Cell Infect Microbiol
  • Dunn et al. 2018 Eat prey, live: Dictyostelium discoideum as a model for cell-autonomous defenses. Front Immunol
  • Cardenal-Muñoz et al. 2017 Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner. PLOS Pathog
  • Barisch & Soldati. 2017 Mycobacterium marinum degrades both triacylglycerols and phospholipids from its Dictyostelium host to synthesise its own triacylglycerols and generate lipid inclusions. PLOS Pathog
  • Delincé et al. 2016 A microfluidic cell-trapping device for single-cell tracking of host-microbe interactions. Lab on a Chip
  • Zhang et al. 2016 Social amoebae trap and kill bacteria by casting DNA nets. Nat Commun




Note for visitors: Please come with a valid identity card

14 Sep

10:30 - 12:00

Seminar room - IPBS - Campus 205