285351 Engineering G-Protein Coupled Receptor Signaling in Yeast

Monday, October 29, 2012: 9:06 AM
Westmoreland West (Westin )
Patrick M. McNeely, Chemical & Biomolecular Engineering, University of Delaware, Newark, DE and Anne S. Robinson, Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE

G Protein-Coupled Receptors (GPCRs) are a large family of integral membrane proteins that transmit extracellular stimuli across the plasma membrane of cells in the human body. This signaling activity has been implicated in numerous diseases and is thus a major target for the development of novel therapeutics [1]. However, drug discovery is challenging because of the paucity of structures and the complex mechanisms for signal transduction in living cells. The ability to express GPCRs in large quantities and study the effect of ligand binding on signaling in a well-controlled manner would enable improved understanding of the biological binding and selectivity mechanisms and improving drug discovery efforts. 

The use of a model cell systems to express and purify recombinant GPCRs is often able to address the quantity of receptor available for study in isolation. To date, however, few systems have been used to directly observe changes in signaling behavior of engineered receptors in these systems. In this work, the yeast Saccharomyces cerevisiae has been engineered to fluorescently report on the signaling activity of the GPCRs expressed in the cell, in addition to expressing recombinant receptor molecules. Using this strain, it is possible to elucidate biomolecular mechanisms of signaling activity in vivo and in membrane-mimetic environments. 

[1] RM Millar and CL Newton, Mol. Endocrinology (2010)

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