Mary Munson, Ph.D.

Vesicle targeting and fusion are tightly regulated processes used by eukaryotic cells to transport cargo between membrane-bound subcellular compartments and to the plasma membrane for secretion. The proper function and specificity of these processes are crucial for maintenance of cellular integrity, normal growth, and for intercellular signaling events, such as neurotransmission. Many key mechanistic issues are poorly understood. What controls the specificity of vesicle targeting to the correct membrane? What determines the site of fusion on the membrane? How are vesicles docked? How are docking and fusion regulated? Our aim is to answer questions such as these through a multifaceted approach that combines biochemical and biophysical techniques with yeast genetics and cell biological methods. We are investigating proteins that regulate exocytosis in the model organism Saccharomyces cerevisiae. Because these proteins are conserved from yeast to man, these studies will advance our understanding of how secretion is regulated in all eukaryotic cells.

Our investigations focus on the Exocyst complex (Fig. 1) which is required for vesicle trafficking in all eukaryotes. The proteins that form the Exocyst complex localize to secretory vesicles and to sites of active secretion at bud tips and mother-bud necks. These proteins are essential for cell viability, they show genetic interactions with the SNAREs and with each other, and their temperature sensitive mutants have secretory blocks and accumulate secretory vesicles. Our research has several aims: 1) biophysical and structural studies of the Exocyst proteins and their interactions with each other; 2) creation and testing of mutants in vivo, in order to elucidate the functions of the Exocyst proteins; 3) characterization of interactions between the Exocyst and other proteins required for exocytosis, such as the SNARE proteins, which are core components of the vesicle fusion machinery, and regulators such as Sec1p and the small GTPase Sec4p; and 4) identification of novel regulators of exocytosis and SNARE complex assembly .

Figure 1. Current model for the architecture of the exocyst complex

Current model for the architecture of the exocyst complex

Office: LRB 905, Lab 970-Y, 940 A
Phone: 508-856-8318
E-mail: Mary.Munson@umassmed.edu
Keywords: Intracellular Trafficking, Biophysics, Cell Biology, Biochemistry, Structural Biology

Regulation of vesicle targeting and fusion