We have recently demonstrated that wild-type β2-adrenergic receptors (β2AR) form homodimers and that disruption of receptor dimerization inhibits signalling via Gs [Hebert, Moffett, Morello, Loisel, Bichet, Barret and Bouvier (1996) J. Biol. Chem. 271, 16384-16392]. Here taking advantage of the altered functional properties of a non-palmitoylated, constitutively desensitized mutant β2AR (C341Gβ2AR), we sought to study whether physical interactions between mutant and wild-type β2AR expressed in Sf9 cells could occur and have functional consequences. Using metabolic labelling with [3H]palmitate and co-immunoprecipitation we demonstrated the existence of heterodimerization between wild-type and C341Gβ2AR. Furthermore, we show that, in co-expression experiments, wild-type receptors have a dominant positive effect resulting in the functional complementation of C341Gβ2AR. Indeed, when expressed alone, the mutant C341G receptor displays altered functional characteristics in that (1) the response of the receptor to agonist is reduced as compared to the wild-type receptor and (2) the desensitization of the receptor in response to prolonged exposure to agonist is minimal. In contrast, when C341G and the wild-type β2AR were expressed together, both the response to agonist and subsequent desensitization (at a constant level of total receptor) were equivalent to the wild-type β2AR expressed alone. This dominant positive effect was also seen when C341G was co-expressed with a second receptor mutant in which the two protein kinase A phosphorylation sites (S261, 262, 345, 346A β2AR) were mutated. Taken together these data suggest that intermolecular interactions between receptors may have both functional and structural implications for G-protein-mediated signalling.
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February 1998
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Research Article|
February 15 1998
Functional rescue of a constitutively desensitized β2AR through receptor dimerization
E. Terence HEBERT;
E. Terence HEBERT
1
*Centre de recherche, Institut de cardiologie de Montréal et Département d'Anésthesie-Réanimation, Université de Montréal, 5000 rue Bélanger est, Montréal, PQ, Canada H1T 1C8
†Département de biochimie et le Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, PQ, Canada H3C 3J7
1To whom correspondence should be addressed.
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P. Thomas LOISEL;
P. Thomas LOISEL
†Département de biochimie et le Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, PQ, Canada H3C 3J7
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Lynda ADAM;
Lynda ADAM
†Département de biochimie et le Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, PQ, Canada H3C 3J7
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Nathalie ETHIER;
Nathalie ETHIER
*Centre de recherche, Institut de cardiologie de Montréal et Département d'Anésthesie-Réanimation, Université de Montréal, 5000 rue Bélanger est, Montréal, PQ, Canada H1T 1C8
†Département de biochimie et le Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, PQ, Canada H3C 3J7
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ST. Stephane ONGE;
ST. Stephane ONGE
†Département de biochimie et le Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, PQ, Canada H3C 3J7
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Michel BOUVIER
Michel BOUVIER
†Département de biochimie et le Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, PQ, Canada H3C 3J7
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Publisher: Portland Press Ltd
Received:
May 14 1997
Revision Received:
October 24 1997
Accepted:
October 27 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 330 (1): 287–293.
Article history
Received:
May 14 1997
Revision Received:
October 24 1997
Accepted:
October 27 1997
Citation
E. Terence HEBERT, P. Thomas LOISEL, Lynda ADAM, Nathalie ETHIER, ST. Stephane ONGE, Michel BOUVIER; Functional rescue of a constitutively desensitized β2AR through receptor dimerization. Biochem J 15 February 1998; 330 (1): 287–293. doi: https://doi.org/10.1042/bj3300287
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