Centre de Recherche
P 514 345-4931, ext. 4190
Chemotaxis is the process that permits directional migration of motile cells in the organism. It is of particular importance during inflammation and the immune response, but also during hematopoiesis. Leukocytes that express given sets of chemokine receptors migrate towards a gradient of corresponding chemokines. Such gradients are maintained, reshaped, and terminated by atypical chemokine scavenger receptors.In the immune system, chemokines are paramount for the homing of immature immune cells to specific niches, their trafficking to secondary lymph organs such as lymph nodes, and effector trafficking to inflamed sites. Therefore, chemokine receptors are potential prime drug targets for the treatment of inflammatory and autoimmune diseases. However, better understanding of the molecular processes underlying their activation seems warranted for the design of optimal therapeutic strategies.Our research deals with structure-function relationships in chemokine receptors, and particularly with conformational changes of the receptor linked to ligand binding. Along the same lines, we investigate synthetic small chemokine receptor ligands of potential therapeutic interest, following the concept of functional selectivity. Our model receptors, CCR2, CXCR4, and CXCR7, are of particular clinical interest due to their respective implication in atherosclerosis, cancer cell survival and metastasis, as well as stem cell homing to bone marrow niches. Moreover, CXCR4 permits the human immunodeficiency virus HIV access to target cells.For these investigations, our laboratory relies mainly on molecular biology techniques, molecular pharmacology, cell biology, and biophysical approaches such as Bioluminescence resonance Energy Transfer (BRET).
- Bonneterre, J., Montpas, N., Boularan, C., Gales, C., and Heveker, N. (2016) Analysis of Arrestin Recrutiment to chemokine receptors by Bioluminscent resonance Enenrgy Transfer Methods in Enzymol 570, 131-153
- Montpas, N., Cabana, J., St-Onge, G., Gravel, S., Morin, G., Kuroyanagi, T., Lavigne, P., Fujii, N., Oishi, S., and Heveker, N. (2015) Mode of binding of the cyclic agonist peptide TC14012 to CXCR7: identification of receptor and compound determinants. Biochemistry 54, 1505-1515
- Berchiche, Y. A., Gravel, S., Pelletier, M. E., St-Onge, G., and Heveker, N. (2011) Different Effects of the Different Natural CC Chemokine Receptor 2b Ligands on beta-Arrestin Recruitment, Galphai Signaling, and Receptor Internalization. Mol Pharmacol 79, 488-498