TY  - GEN
T1  - Methylation of the D2 dopamine receptor affects binding with the human regulatory proteins Par-4 and Calmodulin
AU  - Bowitch, Alexander
AU  - Sahoo, Ansuman
AU  - Clark, Andrea M.
AU  - Ntangka, Christiana
AU  - Raut, Krishna K.
AU  - Gollnick, Paul
AU  - Yu, Michael C.
AU  - Pascal, Steven M.
AU  - Walker, Sarah E.
AU  - Ferkey, Denise M.
DO  - 10.17912/micropub.biology.000366
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000366/
AB  - Protein arginine methylation is a post-translational modification that contributes to the regulation of many cellular processes, including DNA damage repair, transcriptional regulation and protein-protein interaction (Bedford and Richard 2005). In 2003, a large-scale proteomics analysis identified a number of G protein-coupled receptors (GPCRs) as potentially being arginine methylated (Boisvert et al. 2003). However, the effect of methylation on these receptors was not examined. Functional evidence that protein arginine methylation regulates GPCR signaling was first reported for the D2-like dopamine GPCR family (the human D2 and C. elegans DOP-3 receptors) (Likhite et al. 2015), and later for the C. elegans SER-2 tyramine receptor (Bowitch et al. 2018). Protein arginine methyltransferase 5 (PRMT5) methylated a peptide fragment corresponding to a region of the third intracellular loop (3rd ICL) of each of these receptors in vitro, while changing the conserved arginines in this region to alanine reduced receptor methylation (Likhite et al.2015; Bowitch et al. 2018). In cell culture, mutating the conserved putative methylation motif of human D2 decreased signaling via the receptor, leading to a decrease in D2-mediated inhibition of cAMP (Likhite et al. 2015). This, combined with behavioral studies in C. elegans, suggested that protein arginine methylation promotes D2-like dopamine receptor signaling (Likhite et al. 2015). However, the mechanism by which it does so is unknown.
PY  - 2021
JO  - microPublication Biology
ER  -