Strike a pose: Gαq complexes at the membrane

• Gαq and its target proteins signal in a highly membrane-dependent manner.
• The membrane plays a key role in organizing and regulating high-order Gαq assemblies.
• Gαq adopts a similar pose with respect to the membrane when bound to structurally diverse proteins.
• The orientation of Gαq is enforced by multivalent interactions with its targets.

The heterotrimeric G protein Gαq is a central player in signal transduction, relaying signals from activated G-protein-coupled receptors (GPCRs) to effectors and other proteins to elicit changes in intracellular Ca2+, the actin cytoskeleton, and gene transcription. Gαq functions at the intracellular surface of the plasma membrane, as do its best-characterized targets, phospholipase C-β, p63RhoGEF, and GPCR kinase 2 (GRK2). Recent insights into the structure and function of these signaling complexes reveal several recurring themes, including complex multivalent interactions between Gαq, its protein target, and the membrane, that are likely essential for allosteric control and maximum efficiency in signal transduction. Thus, the plasma membrane is not only a source of substrates but also a key player in the scaffolding of Gαq-dependent signaling pathways.