Pharmacology and Chemical Biology
School of Medicine
University of Pittsburgh
Location bias in GPCR signaling
Calcium and phosphate are essential elements for physiological processes ranging from bone formation to nerve transmission and cardiac contractility. The parathyroid hormone (PTH) receptor (PTHR) and calcium-sensing receptor (CaSR) are the major G protein-coupled receptors (GPCRs) regulating the mineral-ion homeostasis. Using pioneering optical techniques, Dr. Vilardaga identified novel molecular, structural, and cellular components in PTHR and CaSR signaling that explain their functions. He discovered a new mechanism of sustained GPCR signaling that involved internalization of the PTH–PTHR complex in endosomes, a process with physiological and disease relevance and shared by other GPCRs. Using cryo-electron microscopy, his team solved high-resolution (3Å) structures of the PTHR in complex with a long-acting signaling PTH analog and the Gs protein. These accomplishments set the stage for developing new targeted small-molecule compounds to treat osteoporosis and mineralization disorders associated with chronic kidney disease.
Visit the Vilardaga lab
Host: Ivet Bahar
Refreshments following the seminar in room 110