Regulation of G Protein-Coupled Receptors (GPCRs) by Protein Arginine Methylation

  Signaling by the neurotransmitter dopamine is important for maintaining diverse physiological functions, including learning, motivation, reward and motor control. Several human disorders, including, schizophrenia, drug addiction and Parkinson’s Disease, have been linked to defects in dopamine signaling. The cellular receptors for dopamine are known as G protein-coupled receptors (GPCRs), which are grouped into two families (D1-like and D2-like) based on their pharmacological properties, sequence conservation, and three-dimensional structure. Signaling by these receptors is highly conserved across eukaryotes.
  My laboratory, in collaboration with that of Dr. Denise Ferkey (University at Buffalo), uncovered a novel role for PRMT5 in promoting dopaminergic signaling by a D2-like dopamine receptor. We plan on further dissecting at the mechanism by which arginine methylation influences dopamine signaling and the extent by which this post-translational modification impacts functioning of GPCRs.