Heterotrimeric G Protein Regulation of Chemotropism in Yeast

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Chemotaxis, or directed cell movement in response to a chemical gradient of a chemoattractant or repellent, plays a vital role in development and immunity. The related phenomenon of chemotropism (directed cell growth in response to a chemical gradient) is integral to the development of the nervous system, blood vessel development, plant pollination and fungal infection. Naturally occurring chemical gradients are very shallow and dynamic. How do cells navigate using such subtle cues? Models of chemotactic phenomena invoke positive feedback loops that amplify small differences in receptor activation across the cell surface into a substantially steeper intracellular signaling gradient. It is presumed that the response of chemotropic cells to shallow chemical gradients is also amplified by interacting feedback loops, but a mechanistic understanding of such loops is lacking. The mating response of the budding yeast Saccharomyces cerevisiae is chemotropic: mating cells interpret complex pheromone gradients and polarize their growth in the direction of the closest partner. Gradient sensing depends on both a surface protein called the pheromone receptor, and an associated protein called Ggamma. Upon pheromone stimulation of the receptor, Ggamma initiates the assembly of numerous proteins into what is known as the chemotropic complex, which catalyzes growth of the cell at the appropriate site. It is not known how the cell senses direction and correctly orients the growth site, and the goal of this project is to understand how yeast cells initiate directional growth toward a mating partner. This investigation will provide a mechanistic understanding of the role that Ggamma phosphorylation plays in the yeast chemotropic response. Because little is known about directional sensing during the chemotropic responses of other eukaryotes, general principles are likely to emerge from this work that will broadly influence the study of chemotropic phenomena.Broader ImpactsThe PI spearheaded the development of and is now administering the NSF/Capstone Undergraduate Research Program for honors students majoring in Biological Sciences at the University of Illinois at Chicago. Students are paired with a mentor for a semester of reading followed by four semesters of research leading to a formal presentation of their work at the annual NSF/Capstone mini-symposium. A minimum of two NSF/Capstone students will work in the PI's lab during the academic year and summertime during this project. The training plan for the postdoctoral fellow on the project includes learning the molecular genetic and imaging methods required in this investigation, mentoring undergraduate and graduate students in biochemical approaches, lecturing in a graduate level signal transduction course, presenting an annual departmental seminar, and developing and funding their own independent research program. Trainees will have an opportunity to undertake research abroad, through collaboration with Dr. Robert Arkowitz (University of Nice, France), a collaborator in this project.