Figure 1.

Structural properties of DREADDs able to selectively activate each of the four major subclasses of heterotrimeric G proteins. The DREADDs shown here are all mutant muscarinic acetylcholine receptors that can be activated by CNO with high potency and efficacy. The red x marks indicate point mutations that prevent acetylcholine from activating these designer receptors (5). The G_q and G_i DREADDs were developed by Armbruster et al. (5). The G_s and G₁₂ DREADDs were generated in the laboratories of Jürgen Wess (6) and Asuka Inoue (7), respectively. Activated G protein α-subunits stimulate or inhibit distinct intracellular effector enzymes or ion channels. This figure represents a modified version of Figure 1 published in (8). Epac, exchange protein activated by cAMP; GIRK, G-protein-regulated inward-rectifier potassium channel; LARG, Leukemia-Associated RhoGEF; PLCβ, phospholipase Cβ; PKA, protein kinase A; PKC, protein kinase C; RhoGEF, Rho guanine nucleotide exchange factor; ROCK, Rho-associated coiled-coil-containing protein kinase; VDCC, voltage-dependent Ca^2+-channel.