TY - JOUR
T1 - G-protein-coupled receptor heterodimerization modulates receptor function
AU - Jordan, Bryen A.
AU - Devi, Lakshmi A.
PY - 1999/6/17
Y1 - 1999/6/17
N2 - The opioid system modulates several physiological processes, including analgesia, the stress response, the immune response and neuroendocrine function. Pharmacological and molecular cloning studies have identified three opioid-receptor types, δ, κ and μ, that mediate these diverse effects. Little is known about the ability of the receptors to interact to form new functional structures, the simplest of which would be a dimer. Structural and biochemical studies show that other G-protein-coupled receptors (GPCRs) interact to form homodimers. Moreover, two non functional receptors heterodimerize to form a functional receptor, suggesting that dimerization is crucial for receptor function. However, heterodimerization between two fully functional receptors has not been documented. Here we provide biochemical and pharmacological evidence for the heterodimerization of two fully functional opioid receptors, κ and δ. This results in a new receptor that exhibits ligand binding and functional properties that are distinct from those of either receptor. Furthermore, the κ-δ heterodimer synergistically binds highly selective agonists and potentiates signal transduction. Thus, heterodimerization of these GPCRs represents a novel mechanism that modulates their function.
AB - The opioid system modulates several physiological processes, including analgesia, the stress response, the immune response and neuroendocrine function. Pharmacological and molecular cloning studies have identified three opioid-receptor types, δ, κ and μ, that mediate these diverse effects. Little is known about the ability of the receptors to interact to form new functional structures, the simplest of which would be a dimer. Structural and biochemical studies show that other G-protein-coupled receptors (GPCRs) interact to form homodimers. Moreover, two non functional receptors heterodimerize to form a functional receptor, suggesting that dimerization is crucial for receptor function. However, heterodimerization between two fully functional receptors has not been documented. Here we provide biochemical and pharmacological evidence for the heterodimerization of two fully functional opioid receptors, κ and δ. This results in a new receptor that exhibits ligand binding and functional properties that are distinct from those of either receptor. Furthermore, the κ-δ heterodimer synergistically binds highly selective agonists and potentiates signal transduction. Thus, heterodimerization of these GPCRs represents a novel mechanism that modulates their function.
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U2 - 10.1038/21441
DO - 10.1038/21441
M3 - Article
C2 - 10385123
AN - SCOPUS:0033578005
SN - 0028-0836
VL - 399
SP - 697
EP - 700
JO - Nature
JF - Nature
IS - 6737
ER -