@farmleap.com
CTO FarmLEAP
General Agricultural and Biological Sciences
Scopus Publications
Maxime Rigo, Myriam Chentouf, André Pèlegrin, and Thierry Chardès
Elsevier BV
Myriam Chentouf, Maxime Rigo, Soufiane Ghannam, Isabelle Navarro-Teulon, Sébastien Mongrand, André Pèlegrin, and Thierry Chardès
Elsevier BV
Myriam Chentouf, Maxime Rigo, Andre Pelegrin, and Thierry Chardes
Bentham Science Publishers Ltd.
Membrane rafts, due to the presence of several immunoreceptors, signal-transducing kinases and lipids such as ceramides which can act as second messengers, play a crucial role in the cell signaling network which fine-tunes various biological effects. The ability of membrane rafts to segregate receptors provides a mechanism for compartmentalization of signaling molecules in plasma membrane by concentrating some components in membrane rafts and excluding others. Based on these observations, the concept of raft-based therapeutics has recently emerged. Raft-targeting molecules can modulate the lipid-protein rheostat of membrane rafts to treat various diseases, such as cancer, neurological disorders or infectious diseases. In this review, we focus on membrane rafts as "discrete" organizing elements of T lymphocytes' plasma membrane and how to reconcile the dynamic nature of membrane rafts with the formation of the immunological synapse. We describe CD4-specific antibodies as prototypical modulators for the disruption of the lipid-protein rheostat in membrane rafts and extend the concept of raft-based therapeutics to other antibodies, sterol- and sphingolipid-modulating drugs, glycerophospholipid analogs, fatty acid modulators, and peptide-derived molecules. This review highlights a novel mode of action of drugs through dietary or therapeutic interventions that target membrane rafts.
Ludivine Leseux, Guy Laurent, Camille Laurent, Maxime Rigo, Amandine Blanc, Daniel Olive, and Christine Bezombes
American Society of Hematology
Previous studies have documented that, in malignant B cells, rituximab elicits a complex and not yet totally understood signaling network contributing to its antitumor effect. In this context, we investigated the role of protein kinase C ζ (PKCζ), an atypical PKC isoform, in the cellular response to rituximab. We found that follicular lymphoma cells displayed an increase in PKCζ expression and activity levels, compared with nonmalignant B cells, and that this enzyme was a critical regulator of the classical MAPK module by stimulating Raf-1 kinase activity. PKCζ appeared to be a significant contributor of abnormal mTOR regulation in follicular lymphoma cells through a MAPK-dependent mechanism. Rituximab was found to inhibit the PKCζ/MAPK/mTOR module in these cells but not in other B-cell lymphomas. Importantly, the expression of a constitutively active form of PKCζ resulted in an efficient protection of these cells toward rituximab. Altogether, our study describes a new regulatory component of mTOR pathway in follicular cell lymphoma and demonstrates that PKCζ is a target for rituximab. Therefore, PKCζ could represent an important parameter for rituximab efficacy and a promising target for future targeted therapy in follicular lymphoma.
Renaud Poincloux, Claire Vincent, Arnaud Labrousse, Jerôme Castandet, Maxime Rigo, Céline Cougoule, Christine Bordier, Véronique Le Cabec, and Isabelle Maridonneau-Parini
Elsevier BV