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G protein-coupled receptors (GPCRs) transmit extracellular signals to the inside by activation of intracellular effector proteins. Different agonists can promote differential receptor-induced signaling responses - termed bias - potentially by eliciting different levels of recruitment of effector proteins. As activation and recruitment of effector proteins might influence each other, thorough analysis of bias is difficult. Here, we compared the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well as arrestin3 binding to the muscarinic acetylcholine receptor M3 by utilizing FRET-based assays. In order to avoid interference between these interactions, we studied GRK2 binding in the presence of inhibitors of Gi and Gq proteins and analyzed arrestin3 binding to prestimulated M3 receptors to avoid differences in receptor phosphorylation influencing arrestin recruitment. We measured substantial differences in the agonist efficacies to induce M3R-arrestin3 versus M3R-GRK2 interaction. However, the rank order of the agonists for G protein- and GRK2-M3R interaction was the same, suggesting that G protein and GRK2 binding to M3R requires similar receptor conformations, whereas requirements for arrestin3 binding to M3R are distinct. Read full article

David Reiner-Link , Alessandro Berghella , Brinda K Rana , G Enrico Rovati , Valerie Capra , Caroline M Person , Abigail Alwin , Campbell Krusemark , Ezequiel Marron Fernandez de Velasco , Steven H Olson , Lauren M Slosky , et. al. GPCR community members Join the GPCR fan club and geek out with fellows! So much more to come!

M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science. M., Marti-Solano, M., Sandhu, M., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023). Kosar, M., Sarott, R. C., Sykes, D. A., Viray, A. E., Vitale, R. M., Tomašević, N., ... & Carreira, E. M. (2024). M., Christopoulos, A., & May, L. T. (2016).

Robert Saddawi-Konefka , Zhiyong Wang , Alexander T Wenzel , Miranda J Song , Meghana S Pagadala , Lauren M Clubb , Joshua Chiou , Sanju Sinha , Marin Matic , Francesco Raimondi , Thomas S Hoang , Rebecca Berdeaux

Lauren M. Slosky About Dr. Lauren M. Slosky Lauren Slosky is an Assistant Professor in the Department of Pharmacology and a member of the Lauren M.

GPCR Podcast << Back to podcast list Lauren Celano About this episode In this special Dr. GPCR podcast episode, we sat down to chat with Lauren Celano to talk about career options for Ph.D.’s Lauren has a science background and is passionate about helping talented scientists find their dream Lauren Celano on the web LinkedIn Propel Careers Email: Lauren@propelcareers.com Dr.