Academic Background

Ph. D. (1980) University of California, Berkeley

Cell-Surface Receptors in Saccharomyces cerevisiae

Our laboratory uses the yeast Saccharomyces cerevisiae as a model system for studying basic problems of hormone receptor function including signal transduction, endocytosis and cellular control of membrane protein integrity. These studies focus on the a-factor pheromone receptor. When a-factor pheromone binds to specific receptors on the surface of yeast cells, it causes the cells to arrest cell division. The occupied receptors are continually internalized and replaced by new receptor synthesis. After prolonged exposure to a-factor, the cells become insensitive to the pheromone and reenter the division cycle. This receptor is a member of the same structural class as the b-adrenergic receptor, photorhodopsin, and a variety of neurotransmitter receptors, that is, all of these receptors contain seven-transmembrane-spanning domains and require a heterotrimeric G protein for signal transduction. The projects in our lab utilize both biochemical and genetic techniques to gain an understanding of the role that cell-surface receptors play in the generation of intracellular signals and the mechanisms by which the cell regulates these signals. Our approach is straightforward. We have designed assays that are sensitive to specific functions of the receptor and the G protein (i.e., ligand binding, receptor conformation, receptor endocytosis and the states of G protein aggregation). Mutations that are defective for one or more of these functions indicate whether the activities have physiological relevance.