Grant: Operating Grant

Dopamine is an important chemical that controls numerous functions in the brain. Dopamine transmits its information via the attachment to proteins called receptors, which are located at the outside of the nerve cells. Humans have five genes coding for dopamine receptors. A faulty activity in dopamine receptors is linked to numerous disorders such as schizophrenia and Parkinson's. Administration of drugs attaching to dopamine receptors that control their activity is currently used to treat schizophrenic and Parkinson's patients. However, these drugs produce unwanted side-effects. Our research focuses on how cells control the dopamine D1 and D5 receptor activity. We will explore the role of a biochemical process called phosphorylation. Phosphorylation is controlled by enzymes termed kinases, which promote the attachment of phosphate to specific spots on proteins. In cells, phosphorylation controls protein activity, transport, recycling and degradation. Specifically, our studies will map the spots on D1 and D5 receptors that are subjected to phosphorylation by different kinases. These studies will uncover the phosphorylation bar codes (also known as "phosphoproteomics") of D1 and D5 receptors. In addition, our work will identify brain proteins that bind to dopamine D1 and D5 receptors to form specific dopamine receptor networks or interactomes. Our research will be conducted using a wide range of techniques such as DNA transfection, immunoprecipitation, whole-cell phosphorylation assay, mass spectrometry and microscopy. A better knowledge of the phosphoproteomics and interactomes of D1 and D5 receptors will help us to better understand how these two receptors work in normal and diseased brains. Most importantly, information gained from our research will be useful in the development of novel drugs and therapeutic approaches for various diseases associated with impairment in dopamine function such as schizophrenia and Parkinson's disease.