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Drs. Denise Ferkey and Michael Yu discover new mechanism of dopamine receptor regulation

A new study published in Science Signaling by the laboratories of Dr. Denise Ferkey and Dr. Michael Yu provides the first direct evidence that G protein-coupled receptors (GPCRs) are functionally regulated by arginine methylation. Specifically, they show that arginines within the third intracellular loop of the human D2 dopamine receptor are methylated by PRMT5, and that this modification enhances D2-like dopamine receptor signaling in both cultured human cells (D2) and in C. elegans (DOP-3). These GPCRs represent the founding members of a new class of proteins that are functionally regulated by arginine methylation. Moreover, their work delineates a new means of regulating G protein-coupled signal transduction. These findings have strong potential to influence the development of a new generation of treatments based on manipulating GPCR methylation status – not only for D2-linked neuropsychiatric disorders, but also for the treatment of diseases ranging from cancer to chronic heart failure.

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Drs. Michael Yu and Denise Ferkey, with lead author Neah Likhite (Ph.D. graduate student)