Engineering GPCR signaling pathways with RASSLs.

Nat Methods
Publication Year: 
Bruce R Conklin
Edward C Hsiao
Sylvie Claeysen
Aline Dumuis
Supriya Srinivasan
John R Forsayeth
Jean-Marc Guettier
W C Chang
Ying Pei
Ken D McCarthy
Robert A Nissenson
Jurgen Wess
Joel Bockaert
Bryan L Roth
PubMed link: 
Public Summary: 
Scientific Abstract: 
We are creating families of designer G protein-coupled receptors (GPCRs) to allow for precise spatiotemporal control of GPCR signaling in vivo. These engineered GPCRs, called receptors activated solely by synthetic ligands (RASSLs), are unresponsive to endogenous ligands but can be activated by nanomolar concentrations of pharmacologically inert, drug-like small molecules. Currently, RASSLs exist for the three major GPCR signaling pathways (G(s), G(i) and G(q)). We review these advances here to facilitate the use of these powerful and diverse tools.