The goal of our research is to understand the molecular mechanisms of drug action at G-protein coupled receptors. We are currently focused on deciphering how GPCRs are organized as macromolecular protein complexes in cell membranes. We recently revealed the alpha1D-adrenergic receptor, a key regulator of cardiovascular, nervous system, and urinary function, associates with the dystrophin-associated protein complex through a PDZ-domain interaction. Proteomic studies identified a novel member of the complex, alpha-catulin. Our current goals are to:
1) Determine the functional importance of alpha-catulin for alpha1D-AR/DAPC signalosome signaling in human cells.
2) Determine how many human GPCRs associate with the alpha-catulin/DAPC.
Understanding how GPCRs are organized as macromolecular complexes in human cells may identify novel drug target interfaces for treating disease.
G-protein coupled receptors (or GPCRs) are targeted by >40% of all OTC and prescribed medications. Common drugs targetting GPCRs include anti-histamines, opioids, beta-adrenergic receptor agonists / antagonists and serotonergics. GPCRs also perceive sensory stimuli, including light in the eye (rhodopsin), smell via olfactory receptors and taste. Many drugs of abuse function through GPCRs, including heroin/morphine (opioid GPCRs), marijuana / THC (cannabinoid GPCRs), as well as LSD and other hallucinogenics (serotonin GPCRs).
Studying GPCRs is important to understand how drugs work in the body, and to permit the creation of efficacious new drugs with limited side effects.