Patrick J. Brennwald, Ph.D.

Research

We have been examining plasma membrane targeting events in the yeast, Saccharomyces cerevisiae, in order to take advantage of the genetic and cell biological tools available in this organism. We have identified and extensively characterized a set of SNARE proteins which are required for cell surface transport in yeast. Our genetic and biochemical analysis of these proteins has led us to the identification of a new regulatory pathway involving the Rho GTPases Cdc42 and Rho3, as well as a novel Sec9 binding protein, related to the Drosophila tumor suppressor lethal giant larvae. Recent work from our lab suggests that Cdc42 function in exocytosis is restricted to very early in bud emergence while Rho3 appears to function in this regard throughout the cell cycle. We are testing the model that the Rho-Cdc42/Sro7/Sec9 pathway is conserved in higher eukaryotic cells including polarized epithelial cells and neurons. This regulation may represent a key mechanism by which eukaryotic cells regulate and coordinate the polarity of the actin cytoskeleton with the polarized delivery of protein and lipid to the cell surface. Finally studies from other systems suggest that loss of function in this pathway may be tied to the loss of polarity commonly observed during tumorigenesis.