D1 and NMDA receptors hook up: expanding on an emerging theme

In the dominant paradigm for functional interactions between G-protein-coupled receptors (GPCRs) and ligand-gated ion channels, the mantra is that the interactions are indirect, indirect, indirect. It is commonly understood that activating GPCRs engages one or more sets of intracellular signaling cascades that indirectly affect the function or localization of a cohort of ligand-gated ion channels. Conversely, stimulating ligand-gated channels, particularly those that are permeable to Ca(2+), indirectly produces effects on GPCRs and/or on GPCR-activated signaling cascades. The foundation of this dichotomous world-view shook (just a little) when it was discovered that D5 dopamine receptors bind directly to GABA(A) receptors, and that this direct interaction reciprocally affects the signaling of both types of receptor. Now, D1 dopamine receptors also have got into the act!