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- Title
The protein arginine methyltransferase PRMT5 promotes D2-like dopamine receptor signaling.
- Authors
Krzyzanowski, Michelle C.; Likhite, Neah; Jackson, Christopher A.; Wood, Jordan F.; Yu, Michael C.; Ferkey, Denise M.; Birkaya, Barbara; Michaels, Kerry L.; Mao-Shih Liang; Lei, Pedro; Andreadis, Stelios T.; Clark, Stewart D.
- Abstract
Protein arginine methylation regulates diverse functions of eukaryotic cells, including gene expression, the DNA damage response, and circadian rhythms. We showed that arginine residues within the third intracellular loop of the human D2 dopamine receptor, which are conserved in the DOP-3 receptor in the nematode Caenorhabditis elegans, were methylated by protein arginine methyl-transferase 5 (PRMT5). By mutating these arginine residues, we further showed that their methylation enhanced the D2 receptor-mediated inhibition of cyclic adenosine monophosphate (cAMP) signaling in cultured human embryonic kidney (HEK) 293T cells. Analysis of prmt-5--deficient worms indicated that methylation promoted the dopamine-mediated modulation of chemosensory and locomotory behaviors in C. elegans through the DOP-3 receptor. In addition to delineating a previously uncharacterized means of regulating GPCR (heterotrimeric guanine nucleotide-binding protein-coupled receptor) signaling, these findings may lead to the development of a new class of pharmacological therapies that modulate GPCR signaling by changing the methylation status of these key proteins.
- Subjects
PROTEIN arginine methyltransferases; GENE expression; DOPAMINE; EUKARYOTIC cells; CYCLIC adenylic acid
- Publication
Science Signaling, 2015, Vol 8, Issue 402, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aad0872