G-protein coupled receptors (GPCRs) bind to extracellular molecules and produce an intracellular downstream signaling response inside the cells. Because of their membrane localization and the ability to produce intracellular changes, they are easy target for therapeutics; approximately 40% of drugs in the market target these receptors. Yeast share many functionally exchangeable proteins with humans involved in the GPCR signaling pathway, and provide a relatively easy and inexpensive platform without the complexities of multiple GPCRs, receptor promiscuity and crosstalk that occurs in native mammalian hosts. The adenosine receptor subfamily (A1R, A2aR, A2bR and A3R) of GPCRs bind the natural ligand adenosine, an important energy metabolite produced under stressful conditions and these receptors help carryout its essential functions in the cells. Adenosine receptors are therapeutic targets for Alzheimer’s disease, Parkinson’s disease and many other diseases. This talk will describe research using chimeric and truncated adenosine receptors expressed in yeast to determine the role of the receptor C-terminus for ligand binding and downstream signaling. These observations were validated in HEK cells, and will be used to highlight the importance of yeast as a platform to study GPCR-ligand binding and downstream signaling.

Yeast as a platform to study adenosine receptor signaling

255th National Meeting (2018)

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