Engineering GPCR signaling pathways with RASSLs.
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.
Conklin
Bruce R
BR
Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, California 94158, USA. bconklin@gladstone.ucsf.edu
Hsiao
Edward C
EC
Claeysen
Sylvie
S
Dumuis
Aline
A
Srinivasan
Supriya
S
Forsayeth
John R
JR
Guettier
Jean-Marc
JM
Chang
W C
WC
Pei
Ying
Y
McCarthy
Ken D
KD
Nissenson
Robert A
RA
Wess
Jürgen
J
Bockaert
Joël
J
Roth
Bryan L
BL
D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D008024:Ligands; D043562:Receptors, G-Protein-Coupled