Introduction
Desensitization limits the duration and magnitude of GPCR signaling, and the machinery that carries it out is itself subject to regulation. This Masterclass examines the basic mechanisms of receptor desensitization and the mechanistic differences between homologous and heterologous desensitization. It then addresses how post-translational modifications regulate the desensitization machinery and alter its function.
Coverage extends to the current state of GPCR desensitization in health and disease, including how certain therapeutics deleteriously regulate this machinery, the consequences for therapeutic efficacy, and strategies to overcome them. Intended for scientists with a working knowledge of GPCR pharmacology whose work involves receptor regulation, loss of response, or sustained therapeutic efficacy.
Instructor
Adriano Marchese's research examines how GPCR signaling is regulated by β-arrestin-dependent and β-arrestin-independent pathways, with the goal of identifying and targeting novel aspects of GPCR signaling for therapeutic development. He is Professor of Biochemistry at the Medical College of Wisconsin in Milwaukee.
His interest in GPCRs is longstanding. During his graduate work at the University of Toronto, where he earned his M.Sc. and Ph.D. in Pharmacology, he worked on the cloning and characterization of genes encoding GPCRs. As a postdoctoral fellow at Thomas Jefferson University, he investigated the mechanisms that regulate GPCR trafficking.
His Masterclass brings this mechanistic view of receptor regulation to the question of how desensitization shapes GPCR signaling in health and disease.