Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function.
In the last four to five years, the view that G protein-coupled receptors (GPCRs) function as monomeric proteins has been challenged by numerous studies, which suggests that GPCRs exist as dimers or even higher-structure oligomers. Recently, biophysical methods based on luminescence and fluorescence energy transfer have confirmed the existence of such oligomeric complexes in living cells. Although no consensus exists on the role of receptor dimerization, converging evidence suggests potential roles in various aspects of receptor biogenesis and function. In several cases, receptors appear to fold as constitutive dimers early after biosynthesis, whereas ligand-promoted dimerization at the cell surface has been proposed for others. The reports of heterodimerization between receptor subtypes suggest a potential level of receptor complexity that could account for previously unexpected pharmacological diversities. In addition to fundamentally changing our views on the structure and activation processes of GPCRs, the concept of homo- and heterodimerization could have dramatic impacts on drug development and screening.
Angers
Stephane
S
Department of Biochemistry and Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, H3C 3J7, Canada. stephane.angers@umontreal.ca
Salahpour
Ali
A
Bouvier
Michel
M
D000818:Animals; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004735:Energy Transfer; D005453:Fluorescence; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D008163:Luminescent Measurements; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction
D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins