Research Interests - Javier Pizarro-Cerda
Ph.D. - Pasteur Institute research Scientist
New signaling pathways involved in the Listeria entry into target cells
This project is realized in collaboration with To Nam Tham (Engineer). In order to better understand the signaling cascades triggered by Listeria during entry into target cells, we have performed a proteomic and functional characterization of phagosomes containing latex beads coated with the Listeria invasion molecules InlA and InlB. A functional assay to investigate lipid kinases has led us to discover the presence of type II phosphatidylinositol 4-kinases (PI4-K) at the membrane of InlB-derived phagosomes. These kinases participate in the production of a pool of phosphatidylinositol-4-phosphate (PI4P) that would not be involved in the formation of phosphatidylinositol-3,4,5-triphosphate (PI3,4,5P3) –which is an upstream effector of Rac for cytoskeletal rearrangements during Listeria entry. Instead, this PI4P pool would be required for the recruitment of still unidentified effectors in a different signaling pathway that are also required for entry. We are investigating at this stage which are this downstream effectors of the type II PI 4-Ks, as well as the molecular events required for their recruitment at the bacterial entry site downstream of the cellular receptor for InlB, the hepatocyte growth factor receptor of Met.
The proteomic characterization of phagosomes containing InlA- and InlB-derived phagosomes identified the presence of several unexpected proteins in the Listeria internalization pathways including the small GTPases Rab10 septin 9, and we are also investigating their participation in the infection process.