Diversifying the repertoire of G protein-coupled receptors through oligomerization
- Paul S.-H. Park*,† and
- Krzysztof Palczewski*,†,‡,§
- Departments of *Ophthalmology, ‡Pharmacology, and §Chemistry, University of Washington, Seattle, WA 98195
Oligomerization of G protein-coupled receptors (GPCRs) has received much attention over the past several years (1, 2). The consequences arising from oligomeric arrangements of GPCRs are proposed to play a central role in signal transduction (3). Except for a few cases (e.g., refs. 4–6), many of the recent studies investigating GPCR oligomerization have involved heterologous expression systems of native and modified receptors (7). The studies by Waldhoer et al. in this issue of PNAS (8) broaden the previous work by placing it in a physiologically relevant context.
The opioid receptors studied by Waldhoer et al. (8) belong to the GPCR superfamily and exist as three types: δ, κ, and μ. All three types have been shown previously to form homooligomers individually and heterooligomers with each other (5, 9–12). Waldhoer et al. demonstrate the existence of a functional heteromer of δ and κ opioid receptors in vivo that localizes specifically in the spinal cord. This study gives credence to the wealth of evidence for GPCR oligomerization in vitro. The δ–κ heteromer has a novel pharmacology and is activated by the heteromer-specific agonist 6′-guanidinonaltrindole (6′-GNTI) (Fig. 1), which illustrates the added diversity offered by heterooligomerization (Fig. 2). The novel pharmacological profile of the δ–κ heteromer and the availability of ligands that are specific to this heterooligomer (13 …
