Peter Novick Professor (Cell Biology) Ph.D., UC Berkeley, 1981

Studies in our Laboratory address the molecular mechanisms underlying cell polarity, particularly as they relate to protein secretion and cell surface growth. We have focused on a set of genes whose products are required specifically for the final stages of the secretory pathway in yeast. We can now define three systems, conserved from yeast to man, that together mediate polarized secretory vesicle delivery, docking and fusion. The first system includes Sec4, Sec2, and the actin based cytoskeleton. Sec4 is a GTP-binding protein that functions as a nucleotide dependent switch on the surface of secretory vesicles. Sec2p appears to couple the activation of Sec4p to the polarized delivery of vesicles to the site of exocytosis. The sites of exocytosisare marked by a large complex of proteins, termed the Exocyst, that is peripherally associated with the plasma membrane. Once vesicles have been properly delivered, the interaction with the plasma membrane is mediated by an integral membrane protein on the vesicle (Snc) and an integral membrane protein on the target membrane (Sso). This protein-protein interaction is regulated by Sec9 and Sec1 in response to Sec4 function. Future studies will be directed at defining the interactions between these different systems.