José-María Trifaró, M.D.
Faculty of Medicine
451 Smyth Road, Ottawa, ON K1H 8M5
Tel.: (613) 562-5448
FAX: (613) 562-5637
Cellular and Molecular Neuropharmacology
The main interest of the group is on the cellular and molecular mechanisms involved in hormone and neurotransmitter secretion. Previous work from the laboratory has involved isolation and characterization of chromaffin cell actin isoforms, myosin, alpha-actinin, tropomyosin isoforms, gelsolin, scinderin, neurofilament subunits, calmodulin and calmodulin-binding proteins. The physico-chemical properties of these proteins have been studied and their cellular localizations revealed by biochemical, immunocytochemical and ultrastructural techniques. Work is presently carried out on the molecular characterization of the exocytotic machinery. Most of the studies are directed to understand the role of the cytoskeleton in neurosecretion. Published work from this laboratory has also demonstrated the presence of a subplasmalemma (cortical) network of actin filaments which acts as a barrier to the movement of secretory vesicles to release sites on the plasma membrane. This work indicates that during cell stimulation, the cortical actin filament network is disassembled and that exocytotic pits are localized in areas of actin disassembly. Scinderin, a Ca2+-dependent actin filament severing protein which is present in cortical areas of secretory cells seems to be involved in the regulation of the dynamic changes occurring in the cortical cytoskeleton during secretion.
Some Selected References
Rodríguez Del Castillo, A., Lemaire, S., Tchakarov, L., Jeyapragasan M., Doucet, J.-P., Vitale, M.L. and Trifaró, J.-M. (1990) Chromaffin cell scinderin, a novel calcium-dependent actin filament severing protein. EMBO J. 9, 43-52.
Vitale, M.L., Rodríguez Del Castillo, A., Tchakarov, L. and Trifaró, J.-M. (1991) Cortical filamentous actin disassembly and scinderin redistribution during chromaffin cell stimulation precedes exocytosis: a phenomenon not exhibited by gelsolin. J. Cell Biol., 113:1057-1067.
Rodríguez Del Castillo, A., Vitale, M.L., and Trifaró, J.-M. (1992) Ca2+ and pH determine the interaction of chromaffin cell scinderin with phosphatidyl inositol 4,5-bisphosphate (PIP2) and its cellular distribution during nicotinic-receptor stimulation and protein kinase C activation. J. Cell Biol. 119:797-810.
Vitale, M.L., Seward, E.P., and Trifaró, J.-M. (1995) Chromaffin cortical actin network dynamics control the size of the release-ready vesicle pool and the initial rate of exocytosis. Neuron 14: 353-363.
Zhang, L., Marcu, M.G., Nau-Schmidt,K., and Trifaró, J.-M.(1996) Recombinant Scinderin Enhances Exocytosis, an Effect Blocked by Two Scinderin-Derived Actin-Binding Peptides and PIP2. Neuron 17: 287-296.