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Patricia DULOR Alain BRISSON Olivier LAMBERT Jochen LANG Pascale SUBRA-PATERNAULT Maria URDACI Marie-Christine DURRIEU Xavier SANTARELLI Gilles GUICHARD Ivan HUC Isabelle BESTEL Juan ELEZGARAY Antoine LOQUET Sophie LECOMTE Reiko ODA Marc BONNEU

Carl Creutz, 20 october 2016, 4 pm, ENSCBP

The seminar will take place, the 20th of october, at 4 pm, at the  ENSCBP amphitheater, Building B,  allée Geoffroy Saint-Hilaire, Pessac.

 

Calcium signaling through the copine family of membrane-binding proteins

 

Carl E. Creutz, Professor

Department of Pharmacology, University of Virginia

 

Abstract

 

 

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

 

Short CV

 

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: a.brisson@cbmn.u-bordeaux.fr

 

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