Mike Forte

Cells frequently communicate with one another by means of signals that are received at the outer, plasma membrane by specific receptor molecules. Once activated, receptors then initiate a series of complex biochemical processes that result in specific cellular responses. A variety of receptor types are used to sense extracellular signals. One type involves a receptor with seven transmembrane domains that couples to an intermediate protein, or G protein, to advance the signal within the cell. Michael Forte and his coworkers focus on these kinds of receptor-mediated signaling events and are trying to determine how they contribute to pathways activated during development. In these studies, the lab uses the fruitfly Drosophila as an experimental system so they can apply the tools of genetics, as well as biochemistry and molecular biology. The results of this work indicate that G protein-coupled signaling is involved in modulating decisions at all stages of development. In addition, intracellular pathways activated by G proteins interact with, and modulate, other pathways activated at the cell membrane by a wide variety of signaling molecules. In a second project, Forte and his colleagues use a simple eukaryote, yeast, as a model system to address the mechanisms used by the evolutionarily conserved BCL2 family of proteins to modulate pathways leading to programmed cell death (PCD). Proteins in this family are thought to be central regulators, acting at or near a point in the PCD pathway that dictates whether or not cells are committed to die. Much recent evidence supports the view that critical life/death decisions are regulated by the interaction of BCL2 family members with mitochondria, yet a detailed understanding of many of the important underlying mechanisms and critical biochemical interactions is lacking. Our goal is to use the genetic and biochemical tools available in yeast identify the mechanisms and interactions that underlie the function of BCL2 family members in caspase-independent cell death pathways. All available evidence strongly indicates that BCL2 family members act directly upon highly conserved mitochondrial components in yeast that correspond exactly to their apoptotic substrates in mammalian cells. Thus, although interactions will be uncovered in yeast, the underlying general hypothesis is that they are reflective of a similar general relationship in mammalian cells.

Gross, A., Pilcher, K., Blachly-Dyson, E., Basso, E., Korsmeyer, S., and Forte, M., Biochemical and Genetic Analysis of the Response of Yeast to Expression of BCL2 Family Members, Mol. Cell. Biology, 20: 3125-3136 (2000).

Wolfgang, W., Roberts, I., Hoskote, A., Jackson, S., and Forte, M., Genetic Analysis of the Drosophila Gs Gene, Genetics 158: 1189-1201 (2001).

Bernardi, P., DiLisa, F., Petronilli, V., and Forte, M., A Mitochondrial Perspective on Cell Death, Trends in Biochem. Sciences., 26: 112-117 (2001).

To contact Dr. Forte directly: forte@ohsu.edu