The seminar will take place, the 20th of october, at 4 pm, at the ENSCBP amphitheater, Building B, allée Geoffroy Saint-Hilaire, Pessac.
Carl E. Creutz, Professor
Department of Pharmacology, University of Virginia
The copines are a family of highly conserved, calcium-dependent, membrane-binding proteins that are broadly expressed in protists, plants, and animals (1,2). They have been hypothesized to regulate signaling in cells by recruiting components of signaling pathways to membrane surfaces in response to calcium mobilization (3).
Two examples will be discussed in the lecture: In cultured human HEK-293 cells copine provides a mechanism for the regulation of signaling from the TNF-alpha cytokine receptor by calcium (4); In murine hippocampal neurons, copine enters the spines on dendrites in a calcium-regulated manner and stabilizes expansion of the spines essential for learning and memory (5). In recent studies we have obtained preliminary evidence that the copines catalyze a novel, nucleotide- and calcium-dependent post translational modification of their target proteins, raising the possibility that their effects on signaling pathways may extend beyond their immediate action of recruiting signaling proteins to membranes. This discovery may open up new opportunities to modulate copine activity in cells through the design of small molecule inhibitors of their catalytic activity. Such agents could be of high specificity since the structural basis of copine catalytic activity is unrelated to that of any other enzyme families.
1. Creutz, C. E., Tomsig, J. L., Snyder, S. L., Gautier, M. C., Skouri, F., Beisson, J., and Cohen, J. (1998) The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans. J Biol Chem 273, 1393-1402
2. Tomsig, J. L., and Creutz, C. E. (2002) Copines: a ubiquitous family of Ca(2+)-dependent phospholipid-binding proteins. Cell Mol Life Sci 59, 1467-1477
3. Tomsig, J. L., Snyder, S. L., and Creutz, C. E. (2003) Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif. J Biol Chem 278, 10048-10054
4. Tomsig, J. L., Sohma, H., and Creutz, C. E. (2004) Calcium-dependent regulation of tumour necrosis factor-alpha receptor signalling by copine. Biochem J 378, 1089-1094
5. Reinhard, J. R., Kriz, A., Galic, M., Angliker, N., Rajalu, M., Vogt, K. E., and Ruegg, M. A. (2016) The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory. Nat Commun 7, 11613
Stanford University, California, B.S. Physics 1969
University of Wisconsin, Madison, M.S. Physics 1970
Johns Hopkins University, Baltimore, Maryland, Ph.D. Biophysics 1976
National Institutes of Health, Bethesda, Maryland, Senior Staff Fellow 1976-1981
Centre de Genetique Moleculaire, CNRS, Gif-sur-Yvette, France, Fogarty Senior International Fellow 1995-1996
Department of Pharmacology, University of Virginia, Professor of Pharmacology 1981-present
Contact: Alain Brisson: email@example.com