Localization of G-protein-coupled receptors within membrane microdomains is associated with differential signalling pathway activation. We have shown that two mouse β3-AR (β3-adrenoceptor) isoforms encoded by alternatively spliced mRNAs differ in their signalling properties; the β3a-AR couples only with Gs, whereas the β3b-AR couples with both Gs and Gi. Our previous studies indicated that the β3a-AR is restrained from coupling with Gi due to the interaction of residues in the C-terminus with other protein(s). We have investigated the hypothesis that the β3a-AR interacts with caveolin. Disruption of caveolae in CHO (Chinese-hamster ovary)-K1 cells expressing wild-type β3a-ARs with filipin III, or mutation of a putative caveolin-binding site in the β3a-AR, causes cAMP accumulation to become PTX (pertussis toxin)-sensitive. Likewise, filipin treatment of mouse brown adipocytes that express endogenous β3a-ARs produces a substantial reduction in agonist-stimulated cAMP production that is rescued by pre-treatment with PTX. These studies suggest that β3a-ARs may be restricted to caveolae and that localization of the receptor may play a specific role in G-protein-mediated signalling.
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November 2007
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Conference Article|
October 25 2007
Functional domains of the mouse β3-adrenoceptor associated with differential G-protein coupling
M. Sato;
M. Sato
1Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia
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D.S. Hutchinson;
D.S. Hutchinson
1Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia
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B.A. Evans;
B.A. Evans
1Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia
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R.J. Summers
R.J. Summers
1
1Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia
1To whom correspondence should be addressed (email roger.summers@med.monash.edu.au).
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Publisher: Portland Press Ltd
Received:
July 17 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (5): 1035–1037.
Article history
Received:
July 17 2007
Citation
M. Sato, D.S. Hutchinson, B.A. Evans, R.J. Summers; Functional domains of the mouse β3-adrenoceptor associated with differential G-protein coupling. Biochem Soc Trans 1 November 2007; 35 (5): 1035–1037. doi: https://doi.org/10.1042/BST0371035
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