Biology of Cell Interactions - CNRS URA 2582  


  HEADProf. DAUTRY-VARSAT Alice / adautry@pasteur.fr
  MEMBERSDr GESBERT Franck / Dr SAUVONNET Nathalie / Dr SUBTIL Agathe / Dr MONTES Pavel
Dr PENNINI Meghan / Prof. LAZAROW Paul / BONCOMPAIN Gaëlle / GRASSART Alexandre / FURTADO Rita


  Annual Report

The research of this unit focuses on (i) the mechanisms of entry, signaling and the intracellular fate of receptors (ii) the mechanisms of entry and development of the intracellular bacterium, Chlamydia.

Receptor dynamics and intracellular traffic

Membrane receptors bind their ligand, are endocytosed, and sorted towards degradation or recycling. Endocytosis modulates the expression of membrane components and their signaling activity.

Endocytosis pathways

Receptor-mediated endocytosis through clathrin-coated pits has been by far the most thoroughly investigated. However, other internalization pathways exist, and we have shown that γc, a member of the type I cytokine receptor family, is internalized by a clathrin-independent pathway. We are investigating the molecular machinery underlying this process. Recent results show that small GTPases, RhoA and Rac1, or the large GTPase dynamin and its partner, cortactin, are involved, providing cross-talk between endocytosis, signal transduction and the actin network.

Sorting of intracellular receptors : a role for ubiquitin

Ubiquitinylation of membrane receptors plays a key role in controlling their turnover. We have shown that cytokine receptors, interleukin-2 receptor β and γc, are ubiquitinylated, and their cell surface expression is regulated by the enzyme pair ubiquitin-ligase/ubiquitin-hydrolase, c-Cbl/Dub2. We are currently working on a novel protein which modifies the ubiquitinylation level of these receptors and regulates their trafficking.

Interactions between Chlamydia and the host

Chlamydiae species pathogenic to humans, mainly Chlamydia trachomatis and Chlamydia pneumoniae, cause a number of diseases, including trachoma, pelvic inflammatory disease and pneumonia. We analyze the mechanisms used by the bacteria to enter cells and utilized by them to sustain their growth.

Systematic search for type III secreted proteins and functional studies

Throughout their cycle in the host cell, chlamydiae remain in a membrane-bound compartment called an inclusion. Both the bacteria and the host cell contribute to the lipid and protein composition of the inclusion membrane. We have shown that chlamydiae use a type III secretion mechanism to deliver proteins into this membrane and into the cell cytosol. We have identified twenty-four new proteins that are secreted by this mechanism. These proteins are very likely to be important in Chlamydia pathogenicity and most of our research is dedicated to understanding their function during infection. Some recent work has focused on the interactions between bacterial proteins anchored in the inclusion membrane and host proteins specialized in membrane compartment recognition and fusion, the SNARE proteins.

Chlamydia pneumoniae and atherosclerosis : clinical studies

There is growing evidence that chronic infection by C. pneumoniae may contribute to the development of atherosclerosis. We have developed a method to detect bacteria on balloons used for coronary angioplasty. This new tool will permit exploration of the possible link between infection and early stages of atherosclerosis. It could help in selecting and following patients for therapeutic trials.

dautry.jpg

Chlamydia infected cell. Bacteria (yellow) develop in a membrane-bound compartment, next to the cell nucleus (blue). We have identified proteins secreted by the bacteria into the cell cytosol (red)



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr