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Creutz, Carl

Carl Creutz

Primary Appointment

Pharmacology

Contact Information

PO Box 800735
Charlottesville, VA 22908
Telephone: 434-924-5029
Fax: 434-982-3878
Email: cec3n@virginia.edu

Research Interests

Calcium-dependent, membrane-binding proteins and mechanisms of exocytosis

Research Description

Our research group is studying the subcellular mechanisms that underlie the release of hormones and neurotransmitters by exocytosis. In this process a secretory vesicle moves through the cytoplasmic matrix and attaches to the plasma membrane of the cell. Then the membranes of the vesicle and the cell fuse and the contents of the vesicle are released. Subsequently, the vesicle membrane is recovered by endocytosis and degraded or reused to form new secretory vesicles. Our interests have focused on proteins that may regulate or mediate individual steps in this process. In particular, we are studying a novel group of calcium-dependent, membrane-binding proteins that can promote membrane fusion in vitro. This group of proteins, collectively called the annexins, includes synexin, calpactin, lipocortin, and several other members that have been proposed to mediate calcium-dependent events on membrane surfaces. (For a historical review see: https://pdfs.semanticscholar.org/a221/27aab83c1e0a8aced19b2c635d65d88a061e.pdf ). More recently we have extended our studies to the synaptotagmins and the copines, proteins that interact with membranes through a domain homologous to the calcium- and lipid-binding domain of protein kinase C. In these studies we draw on techniques from biophysics, biochemistry, molecular biology and genetics. For example, we use fluorescence resonance energy transfer techniques to monitor protein-membrane interactions, membrane fusion, and protein self-assembly on membrane surfaces. We use site-directed mutagenesis and bacterial or yeast expression of recombinant proteins to assess the role of particular protein structural domains in promoting membrane fusion. We use cultured bovine chromaffin cells and in vitro kinase assays to assess the role of phosphorylation in regulating annexin function. We use yeast and nematode genetics to analyze the function of calcium-dependant, membrane-binding proteins in the secretory pathway. These fundamental studies on the mechanism of exocytosis may provide a basis for understanding the action of drugs that affect hormone or neurotransmitter release, and may also lead to the development of new pharmacological agents that influence these processes.

Selected Publications

Creutz CE, Hira JK, Gee VE, Eaton JM, Protection of the membrane permeability barrier by annexins., 2012; Biochemistry. 51(50) 9966-83 PMID: 23190562 |

Creutz CE, Novel protein ligands of the annexin A7 N-terminal region suggest pro-beta helices engage one another with high specificity., 2010; General physiology and biophysics. 28() F7-F13 PMID: 20093729 | PMCID: PMC2931597

Creutz CE, Edwardson JM, Organization and synergistic binding of copine I and annexin A1 on supported lipid bilayers observed by atomic force microscopy., 2009; Biochimica et biophysica acta. 1788(9) 1950-61 PMID: 19539605 |

Ramsey CS, Yeung F, Stoddard PB, Li D, Creutz CE, Mayo MW, Copine-I represses NF-kappaB transcription by endoproteolysis of p65., 2008; Oncogene. 27(25) 3516-26 PMID: 18212740 |

Creutz CE, Snyder SL, Interactions of annexins with the mu subunits of the clathrin assembly proteins., 2005; Biochemistry. 44(42) 13795-806 PMID: 16229469 |

Creutz CE, Snyder SL, Schulz TA, Characterization of the yeast tricalbins: membrane-bound multi-C2-domain proteins that form complexes involved in membrane trafficking., 2004; Cellular and molecular life sciences : CMLS. 61(10) 1208-20 PMID: 15141306 |

Tomsig JL, Sohma H, Creutz CE, Calcium-dependent regulation of tumour necrosis factor-alpha receptor signalling by copine., 2003; The Biochemical journal. 378(0) 1089-94 PMID: 14674885 | PMCID: PMC1224034

Creutz CE, Tomsig JL, Snyder SL, Gautier MC, Skouri F, Beisson J, Cohen J, The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans., 1998; The Journal of biological chemistry. 273(3) 1393-402 PMID: 9430674 |

Creutz CE, Snyder SL, Daigle SN, Redick J, Identification, localization, and functional implications of an abundant nematode annexin., 1996; The Journal of cell biology. 132(6) 1079-92 PMID: 8601586 | PMCID: PMC2120750

Damer CK, Creutz CE, Synergistic membrane interactions of the two C2 domains of synaptotagmin., 1994; The Journal of biological chemistry. 269(49) 31115-23 PMID: 7983052 |

Creutz CE, The annexins and exocytosis., 1992; Science (New York, N.Y.). 258(5084) 924-31 PMID: 1439804 |