Picture courtesy of
Dr. Edward Arnold (Rutgers University)

Center for Molecular Biophysics
& Biophysical Chemistry
Rutgers University
610 Taylor Road
Piscataway, NJ 08854

Phone: 732/445-6376

Fax: 732/445-1493

Chavela M. Carr
Assistant Professor
Department of Pathology and Laboratory Medicine, UMDNJ
732-235-2889
675 Hoes Lane; Piscataway, Room 235

In order to uncover the mechanism that controls membrane fusion in cells, our lab focuses on the conserved protein machinery required for secretory vesicle fusion at the plasma membrane, during exocytosis.

Membrane fusion is a mechanism used by biological systems to transfer materials between compartments. Enveloped viruses, such as influenza virus, HIV, and oncogenic retroviruses gain entry into the host cell by fusion of the viral and host cell membranes. Eukaryotic cells use membrane fusion to transport materials between organelles and to expand the cell surface, for cell growth. Specialized endocrine cells signal cell proliferation by secretion of growth factors, and neurons communicate by rapid exocytosis of neurotransmitters into the synapse. In each case, accuracy of material transfer relies on the convergence of multiple factors to stimulate membrane fusion at the correct time and place.

Structurally similar proteins catalyze both viral and intracellular fusion reactions, presumably using a similar mechanism. In both cases, in order to become active, the membrane fusion proteins must undergo specific conformational changes. Whereas much progress has been made in describing the activation of several viral membrane fusion proteins, activation of intracellular fusion proteins, known as SNAREs, remains a puzzle.

In addition to the SNAREs, intracellular membrane fusion reactions require at least a dozen other conserved proteins. Among these, the Sec1 protein is most likely to activate SNAREs for membrane fusion. Vesicle fusion is blocked when the Sec1 protein is defective, yet the molecular function of Sec1 proteins is poorly understood. Our lab uses the genetically and biochemically accessible eukaryote, Saccharomyces cerevisiae to determine the role of Sec1 and other proteins in membrane fusion. Experiments are designed to isolate functional Sec1 protein, to characterize structurally the binding interaction between the Sec1 protein and SNAREs, and to reconstitute the function of the Sec1 protein in SNARE activation and membrane fusion. These studies will be extended to other Sec1 homologs to determine whether or not all intracellular membrane fusion reactions require a Sec1 protein and, if so, whether or not the mechanism of action is general or specialized for membrane fusion at distinct compartments in the cell.